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| Combined Immunodeficiency v1.66 | TKFC |
Zornitza Stark changed review comment from: Single individual reported with homozygous variant. Sources: Literature; to: Single individual reported with homozygous variant. Note relationship with syndromic ID also postulated. Sources: Literature |
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| Combined Immunodeficiency v1.66 | TKFC |
Zornitza Stark gene: TKFC was added gene: TKFC was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TKFC were set to 38697782 Phenotypes for gene: TKFC were set to Inborn error of immunity, MONDO:0003778, TKFC-related Review for gene: TKFC was set to RED Added comment: Single individual reported with homozygous variant. Sources: Literature |
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| Combined Immunodeficiency v1.65 | POLD1 | Zornitza Stark Phenotypes for gene: POLD1 were changed from Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Immunodeficiency 120, MIM# 620836; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.61 | LCP1 | Zornitza Stark Phenotypes for gene: LCP1 were changed from lymphopaenia and neutropaenia to Bone marrow failure syndrome, MONDO:0000159, LCP1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.59 | LCP1 | Zornitza Stark reviewed gene: LCP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Bone marrow failure syndrome, MONDO:0000159, LCP1-related; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.58 | POLD1 | Zornitza Stark Phenotypes for gene: POLD1 were changed from Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.52 | SLC19A1 |
Paul De Fazio gene: SLC19A1 was added gene: SLC19A1 was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: SLC19A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC19A1 were set to 36517554,36745868 Phenotypes for gene: SLC19A1 were set to Combined immunodeficiency, SLC19A1-related MONDO:0015131 Review for gene: SLC19A1 was set to GREEN gene: SLC19A1 was marked as current diagnostic Added comment: PMID: 36745868 report two distantly related patients (last common ancestor 5 generations prior) with the same homozygous missense variant, G348R. The variant is absent from gnomAD, although the residue is not conserved in mammals. Both patients experienced severe recurrent infection, neurologic and hematologic disorders, and gastroenteropathy. Functional studies on patient lymphocytes were consistent with reduced transporter activity. PMID: 36517554 report two cousins with immunodeficiency with the same G348R variant as above. Functional studies on patient cells supported loss of transporter function. The patient’s symptoms ameliorated, and hematological and immunological tests normalized in the 2nd month of folinic acid supplementation. Sources: Literature |
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| Combined Immunodeficiency v1.51 | RELB | Peter McNaughton reviewed gene: RELB: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36402602; Phenotypes: Complex autoimmunity; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.51 | ARPC5 | Zornitza Stark Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.48 | IRF4 | Zornitza Stark Phenotypes for gene: IRF4 were changed from Combined immunodeficiency to Combined immunodeficiency, MONDO:0015131, IRF4-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.44 | ERBIN | Zornitza Stark Phenotypes for gene: ERBIN were changed from Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some to Combined immunodeficiency, MONDO:0015131, ERBIN-related; Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.43 | ERBIN | Zornitza Stark edited their review of gene: ERBIN: Changed phenotypes: Combined immunodeficiency, MONDO:0015131, ERBIN-related, Recurrent respiratory infections, Susceptibility to S.aureus, Eczema, Hyperextensible joints, Scoliosis, Arterial dilatation in some | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.43 | REL | Peter McNaughton reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34623332; Phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.43 | RELA | Zornitza Stark Publications for gene: RELA were set to 28600438; 29305315 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.42 | RELA | Zornitza Stark Classified gene: RELA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.42 | RELA | Zornitza Stark Gene: rela has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.41 | RELA | Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from five families reported.; Changed rating: GREEN; Changed publications: 28600438, 29305315, 37273177; Changed phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287, Impaired NFkB activation, reduced production of inflammatory cytokines, autoimmune cytopaenias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.39 | ARPC5 |
Paul De Fazio gene: ARPC5 was added gene: ARPC5 was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARPC5 were set to 37349293; 37382373 Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131 Review for gene: ARPC5 was set to GREEN gene: ARPC5 was marked as current diagnostic Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable. PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed. PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect). Functional studies and a mouse model were supportive of the disease association. Sources: Literature |
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| Combined Immunodeficiency v1.39 | NFATC1 | Zornitza Stark Phenotypes for gene: NFATC1 were changed from Combined Immune deficiency to Inborn error of immunity, MONDO:0003778, NFATC1-related; Combined Immune deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.32 |
Zornitza Stark HPO terms changed from to Combined immunodeficiency, HP:0005387 List of related panels changed from to Combined immunodeficiency; MONDO:0015131; Combined immunodeficiency; HP:0005387 |
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| Combined Immunodeficiency v1.31 | LCP2 |
Peter McNaughton gene: LCP2 was added gene: LCP2 was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: LCP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LCP2 were set to PMID: 36474126; PMID: 33231617 Review for gene: LCP2 was set to GREEN Added comment: 3-year-old child who was born to first-cousins parents and presented with recurrent infections, failure to thrive, and severe EBV-related infection and lymphoproliferation. Functional testing linking gene with impaired t cell signalling. Previous unrelated patient reported in PMID: 33231617 with SCID phenotype. Sources: Literature |
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| Combined Immunodeficiency v1.30 | CHUK |
Zornitza Stark gene: CHUK was added gene: CHUK was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: CHUK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHUK were set to 34533979 Phenotypes for gene: CHUK were set to Combined immunodeficiency, MONDO:0015131, CHUK-related Review for gene: CHUK was set to AMBER Added comment: PMID 34533979: single individual reported with homozygous missense variant in this gene and recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine. Supportive functional data. Sources: Literature |
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| Combined Immunodeficiency v1.20 | COPG1 | Zornitza Stark reviewed gene: COPG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33529166; Phenotypes: Combined immunodeficiency MONDO:0015131, COPG1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.20 | COPG1 | Zornitza Stark Phenotypes for gene: COPG1 were changed from Combined immunodeficiency MONDO:0015131, COPG1-related to Combined immunodeficiency MONDO:0015131, COPG1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.19 | COPG1 | Zornitza Stark Phenotypes for gene: COPG1 were changed from Combined Immune deficiency to Combined immunodeficiency MONDO:0015131, COPG1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.17 | MAN2B2 | Zornitza Stark Phenotypes for gene: MAN2B2 were changed from Combined Immune deficiency to Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Combined Immune deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.15 | MAN2B2 | Zornitza Stark reviewed gene: MAN2B2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.4 | REL | Zornitza Stark Phenotypes for gene: REL were changed from Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity to Immunodeficiency 92, MIM# 619652; Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.3 | REL | Zornitza Stark Publications for gene: REL were set to 31103457 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.2 | REL | Zornitza Stark Classified gene: REL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.2 | REL | Zornitza Stark Gene: rel has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.2 | REL | Zornitza Stark Classified gene: REL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.2 | REL | Zornitza Stark Gene: rel has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v1.1 | REL |
Zornitza Stark edited their review of gene: REL: Added comment: Second unrelated individual reported, with a different homozygous splice site variant. Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; Changed rating: AMBER; Changed publications: 31103457, 34623332; Changed phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity |
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| Combined Immunodeficiency v0.387 | RTEL1 | Zornitza Stark Phenotypes for gene: RTEL1 were changed from to Dyskeratosis congenita, autosomal dominant 4 MIM# 615190; Dyskeratosis congenita, autosomal recessive 5 MIM# 615190; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 MIM# 616373 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.381 | IKBKG |
Danielle Ariti edited their review of gene: IKBKG: Added comment: Ectodermal dysplasia with immunodeficiency Over 12 families have been identified with IKBKG variants Individuals typically present within the first year of life with recurrent infections (pneumonia, bacterial infections of the bone and soft tissue), elevated IgM and ectodermal dysplasia features (sparse scalp and body hair, reduced ability to sweat, and conical teeth) ------ Immunodeficiency-33 and no ectodermal dysplasia 10 unrelated individuals been reported with IKBKG variants Characterised by early-onset severe infections, hypogammaglobulinaemia, decreased IgG and impaired antibody response to multiple vaccinations. ------- Multiple null IKBKG mouse models demonstrating both disease phenotypes AND Hemizygous (insertion, slice site, deletion and missense) variants have been reported in association with both diseases, causing premature stop codons; most common variants are splice-site; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females |
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| Combined Immunodeficiency v0.381 | CD40LG |
Danielle Ariti changed review comment from: Well-established gene-disease association; more than 20 unrelated individuals and multiple CD40LG deficient mouse models demonstrate an association with X-linked recessive hyper IgM syndrome. Heterozygous females are characteristically asymptomatic (normal immunoglobulin levels); however, there have been rare cases of affected females expressing clinical phenotypes due to skewed X-chromosome inactivation (PMID: 16311023 & 9933119) Variants identified include missense, in-frame indel, nonsense, frameshift, large deletion and complex rearrangements resulting in LOF. Typical immunological profile includes decreased IgG/IgA/IgE levels with normal-increased IgM levels, resulting in susceptibility to severe and opportunistic viral/bacterial infections.; to: Well-established gene-disease association; more than 20 unrelated individuals and multiple CD40LG deficient mouse models demonstrate an association with X-linked recessive hyper IgM syndrome. Heterozygous females are characteristically asymptomatic (normal immunoglobulin levels); however, there have been rare cases of affected females expressing clinical phenotypes due to skewed X-chromosome inactivation (PMID: 16311023 & 9933119) Variants identified include missense, in-frame indel, nonsense, frameshift, large deletion and complex rearrangements resulting in LOF. Typical immunological profile includes decreased IgG/IgA/IgE levels with normal-increased IgM levels, resulting in susceptibility to severe and opportunistic viral/bacterial infections. |
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| Combined Immunodeficiency v0.378 | RTEL1 | Danielle Ariti reviewed gene: RTEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301779, 23329068, 15210109, 23453664, 19461895, 25848748, 25607374; Phenotypes: Dyskeratosis congenita, autosomal dominant 4 MIM# 615190, Dyskeratosis congenita, autosomal recessive 5 MIM# 615190, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 MIM# 616373; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.365 | RAC2 |
Danielle Ariti changed review comment from: Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis 2 unrelated individuals; mono-allelic; loss of function; One mouse model; functional studies Both individuals carried a de novo heterozygous missense variant (p.Asp57Asn), resulting in an impaired GTP binding domain and loss of function. Both individuals presented from birth with recurrent perirectal/ paratracheal abscesses, failure to heal surgical wounds, and the absence of pus in infected areas, in addition to leukocytosis and neutrophilia. -------- Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia Only one family (2 sibs) has been reported; bi-allelic; loss of function; one mouse model. They were homozygous for a nonsense variant p.Trp56Ter (W56X), resulting in premature termination and loss of function. Clinical history included recurrent respiratory infections leading to the development of bronchiectasis, urticaria, factor XI deficiency, and hypothyroidism. Their immunologic presentation showed a progression from selective IgA deficiency to Hypogammaglobulinaemia of all classes leading to a diagnosis of CVID. --------- Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia 13 individuals from 8 unrelated families; mono-allelic; gain of function; multiple mouse models Mono-allelic missense variants were reported in each individual (5 x De Novo) and resulted in a gain-of -function. (E62K, P34H, N92T, G12R) These individuals typically presented in infancy with frequent infections, profound leukopaenia, lymphopaenia diarrhoea and hypogammaglobulinaemia. ----- Amber- Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis (loss of function) Amber- Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia (loss of function) Green- Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia (gain of function); to: Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis 2 unrelated individuals; mono-allelic; loss of function; One mouse model; functional studies Both individuals carried a de novo heterozygous missense variant (p.Asp57Asn), resulting in an impaired GTP binding domain and loss of function. Both individuals presented from birth with recurrent perirectal/ paratracheal abscesses, failure to heal surgical wounds, and the absence of pus in infected areas, in addition to leukocytosis and neutrophilia. -------- Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia Only one family (2 sibs) has been reported; bi-allelic; loss of function; one mouse model. They were homozygous for a nonsense variant p.Trp56Ter (W56X), resulting in premature termination and loss of function. Clinical history included recurrent respiratory infections leading to the development of bronchiectasis, urticaria, factor XI deficiency, and hypothyroidism. Their immunologic presentation showed a progression from selective IgA deficiency to Hypogammaglobulinaemia of all classes leading to a diagnosis of CVID. --------- Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia 13 individuals from 8 unrelated families; mono-allelic; gain of function; multiple mouse models Mono-allelic missense variants were reported in each individual (5 x De Novo) and resulted in a gain-of -function. (E62K, P34H, N92T, G12R) These individuals typically presented in infancy with frequent infections, profound leukopaenia, lymphopaenia diarrhoea and hypogammaglobulinaemia. ----- Amber- Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis (Mono-allelic; loss of function) Red- Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia (Bi-allelic; loss of function) Green- Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia (Mono-allelic; gain of function) |
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| Combined Immunodeficiency v0.309 | STAT3 |
Danielle Ariti changed review comment from: Well-established disease-gene association for hyper-IgE syndrome; identified heterozygous STAT3 variants in over 50 familial and sporadic cases; dominant-negative loss of function; multiple mouse models Hyper IgE individuals presented with the triad of staphylococcal abscesses, pneumonia with pneumatocele formation, and extremely elevated IgE. 15 unrelated families with Autoimmune disease, multisystem, infantile-onset, 1; 13 STAT3 variants identified (5 were de novo); gain of function; multiple mouse models Autoimmune disease, multisystem, infantile-onset, 1 individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature. STAT3 monoallelic variants were missense and in-frame deletions in both diseases. (Hyper IgE- Loss of Function AND Autoimmune disease- Gain of function); to: Well-established disease-gene association for hyper-IgE syndrome; identified heterozygous STAT3 variants in over 50 familial and sporadic cases; dominant-negative loss of function; multiple mouse models Hyper IgE individuals presented with the triad of staphylococcal abscesses, pneumonia with pneumatocele formation, and extremely elevated IgE. 15 unrelated families with Autoimmune disease, multisystem, infantile-onset, 1; 13 STAT3 variants identified (5 were de novo); gain of function; multiple mouse models Autoimmune disease, multisystem, infantile-onset, 1 individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature. STAT3 monoallelic variants were missense and in-frame deletions in both diseases. (Hyper IgE- Loss of Function AND Autoimmune disease- Gain of function) |
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| Combined Immunodeficiency v0.309 | STAT3 |
Danielle Ariti edited their review of gene: STAT3: Added comment: 18 individuals from 15 unrelated families; Multiple mouse models All 13 heterozygous variants reported have been missense or in-frame deletions that result in a gain of function; 5 of these de novo Individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature.; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 25349174, 25038750, 25359994, 16783372; Changed phenotypes: Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952, Lymphoproliferation, solid organ autoimmunity, recurrent infections, short stature, eczema, delayed puberty, dental abnormalities, autoimmune cytopaenias, juvenile-onset arthritis, primary hypothyroidism |
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| Combined Immunodeficiency v0.268 | NFKBIA |
Danielle Ariti changed review comment from: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual). Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity. The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).; to: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual). Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity. The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands). |
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| Combined Immunodeficiency v0.268 | LRBA |
Danielle Ariti changed review comment from: Over 10 unrelated individuals with LRBA variants displaying immunodeficiency phenotype; one mouse model. Reported homozygous truncating variants (missense/ nonsense). Most reported individuals displayed reduced IgG and IgA, autoimmune disorders, hypogammaglobulinemia and recurrent infections.; to: Over 10 unrelated individuals with LRBA variants displaying immunodeficiency phenotype; one mouse model. Reported homozygous truncating variants (missense/ nonsense). Most reported individuals displayed reduced IgG and IgA, autoimmune disorders, hypogammaglobulinaemia and recurrent infections. |
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| Combined Immunodeficiency v0.259 | MALT1 |
Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency. Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains. All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN |
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| Combined Immunodeficiency v0.251 | IL7R |
Danielle Ariti changed review comment from: 6 unrelated individuals with 9 unique variants (missense, splicing, nonsense, and frameshift) have been reported). Two IL7R null mice models demonstrating a phenotype consistent with T cell Lymphopaenia Typical patient immunological phenotype consisted of Low B-cells, decreased immunoglobulins with normal-high B/NK cell numbers.; to: 6 unrelated individuals with 9 unique variants (missense, splicing, nonsense, and frameshift) have been reported. Two IL7R null mice models demonstrating a phenotype consistent with T cell Lymphopaenia Typical patient immunological phenotype consisted of Low B-cells, decreased immunoglobulins with normal-high B/NK cell numbers. |
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| Combined Immunodeficiency v0.232 | ICOS |
Danielle Ariti changed review comment from: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models. Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion. Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA. However, phenotypic expression is highly variable, with some individuals only displaying immunological phenotypes.; to: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models. Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion. Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA. However, phenotypic expression is highly variable, with some individuals only displaying immunological phenotypes. |
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| Combined Immunodeficiency v0.232 | CD3G |
Danielle Ariti changed review comment from: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models. All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features, whilst other CD3G-deficient individuals were in healthy condition decades into life. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins.; to: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models. All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features, whilst other CD3G- deficient individuals only display immunological phenotype and no other features. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins. |
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| Combined Immunodeficiency v0.232 | CD27 |
Danielle Ariti changed review comment from: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic or display borderline-low hypogammaglobulinaemia.; to: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic-borderline low hypogammaglobulinaemia. |
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| Combined Immunodeficiency v0.229 | DKC1 |
Danielle Ariti changed review comment from: More than 20 affected unrelated individuals have been reported; multiple mouse models. Heterozygous non-frameshift deletion variants and missense variants have been identified in DKC1 in these individuals, including the most common p.Ala353Val. Typically presents with abnormal skin pigmentation, nail dystrophy, oral leukoplakia, bone marrow failure and immunodeficiencies. PMID: 9663235 (1998) partial expression in heterozygous females displayed early pigmentary skin changes; to: More than 20 affected unrelated individuals have been reported; multiple mouse models. Heterozygous deletion variants and missense variants have been identified in DKC1 in these individuals, including the most common p.Ala353Val. Typically presents with abnormal skin pigmentation, nail dystrophy, oral leukoplakia, bone marrow failure and immunodeficiencies. PMID: 9663235 (1998) partial expression in heterozygous females displayed early pigmentary skin changes |
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| Combined Immunodeficiency v0.197 | AK2 |
Danielle Ariti changed review comment from: PMID: 19043417. 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance. PMID: 19043416. 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.; to: PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance. PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals. Sources: Literature |
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| Combined Immunodeficiency v0.196 | SASH3 |
Zornitza Stark gene: SASH3 was added gene: SASH3 was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SASH3 were set to 33876203 Phenotypes for gene: SASH3 were set to Combined immunodeficiency; immune dysregulation Review for gene: SASH3 was set to GREEN Added comment: Four unrelated males reported presenting with combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopaenias. One missense variant, rest were nonsense. Sources: Literature |
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| Combined Immunodeficiency v0.191 | KMT2A |
Bryony Thompson gene: KMT2A was added gene: KMT2A was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KMT2A were set to 32048120; 28623346; 27320412 Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome MIM#605130 Review for gene: KMT2A was set to AMBER Added comment: 4 cases with combined immunodeficiency from 2 unrelated families. Sources: Expert list |
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| Combined Immunodeficiency v0.180 | RNU4ATAC |
Bryony Thompson gene: RNU4ATAC was added gene: RNU4ATAC was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU4ATAC were set to 32048120; 26522830; 29265708 Phenotypes for gene: RNU4ATAC were set to Lowry-Wood syndrome MIM#226960; Microcephalic osteodysplastic primordial dwarfism, type I MIM#210710; Roifman syndrome MIM#616651 Review for gene: RNU4ATAC was set to GREEN gene: RNU4ATAC was marked as current diagnostic Added comment: Conditions caused by this gene are classified as Immuno-osseus dysplasias by IUIS (under CID with syndromic features). >3 unrelated cases have been reported. Sources: Expert list |
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| Combined Immunodeficiency v0.172 | TLR8 |
Zornitza Stark gene: TLR8 was added gene: TLR8 was added to Combined Immunodeficiency. Sources: Literature somatic tags were added to gene: TLR8. Mode of inheritance for gene: TLR8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TLR8 were set to 33512449 Phenotypes for gene: TLR8 were set to Immunodeficiency; bone marrow failure Mode of pathogenicity for gene: TLR8 was set to Other Review for gene: TLR8 was set to GREEN Added comment: Six unrelated males reported with a phenotype comprising neutropaenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure. Three different variants reported, the variant was somatic in 5/6 individuals. GoF mechanism demonstrated. Sources: Literature |
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| Combined Immunodeficiency v0.164 | FNIP1 |
Zornitza Stark gene: FNIP1 was added gene: FNIP1 was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FNIP1 were set to 32181500; 32905580 Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia Review for gene: FNIP1 was set to GREEN Added comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed. - PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway. Sources: Literature |
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| Combined Immunodeficiency v0.162 | MYSM1 |
Zornitza Stark changed review comment from: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay Sources: Expert list; to: Early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay. At least 4 unrelated families reported. Sources: Expert list |
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| Combined Immunodeficiency v0.160 | IVNS1ABP |
Bryony Thompson gene: IVNS1ABP was added gene: IVNS1ABP was added to Combined Immunodeficiency. Sources: Literature Mode of inheritance for gene: IVNS1ABP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IVNS1ABP were set to 32499645 Phenotypes for gene: IVNS1ABP were set to Primary immunodeficiency Review for gene: IVNS1ABP was set to GREEN Added comment: 3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes. Sources: Literature |
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| Combined Immunodeficiency v0.97 | IL6ST |
Zornitza Stark changed review comment from: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association. Sources: Expert list; to: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association. 2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed. Sources: Expert list |
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| Combined Immunodeficiency v0.82 | NFE2L2 |
Zornitza Stark gene: NFE2L2 was added gene: NFE2L2 was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NFE2L2 were set to 29018201 Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744; Recurrent respiratory and skin infection; Growth retardation; Developmental delay, borderline ID; White matter cerebral lesions Review for gene: NFE2L2 was set to GREEN Added comment: Four unrelated individuals reported. Sources: Expert list |
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| Combined Immunodeficiency v0.76 | SKIV2L |
Zornitza Stark gene: SKIV2L was added gene: SKIV2L was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: SKIV2L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SKIV2L were set to 22444670 Phenotypes for gene: SKIV2L were set to Trichohepatoenteric syndrome 2, MIM# 614602; Respiratory infections; IUGR; Facial dysmorphic features; Wooly hair; Early-onset intractable diarrhoea; Liver cirrhosis; Platelet abnormalities Review for gene: SKIV2L was set to GREEN Added comment: At least six unrelated individuals reported. Sources: Expert list |
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| Combined Immunodeficiency v0.66 | IL6R |
Zornitza Stark gene: IL6R was added gene: IL6R was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: IL6R was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6R were set to 31235509 Phenotypes for gene: IL6R were set to Recurrent pyogenic infections, cold abscesses; High circulating IL-6 levels; High IgE Review for gene: IL6R was set to AMBER Added comment: Two unrelated individuals reported, some functional data. Sources: Expert list |
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| Combined Immunodeficiency v0.57 | REL | Zornitza Stark Marked gene: REL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.57 | REL | Zornitza Stark Gene: rel has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.57 | REL |
Zornitza Stark gene: REL was added gene: REL was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REL were set to 31103457 Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity Review for gene: REL was set to RED Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data. Sources: Expert list |
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| Combined Immunodeficiency v0.53 | RELA | Zornitza Stark Marked gene: RELA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.53 | RELA | Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.53 | RELA | Zornitza Stark Classified gene: RELA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.53 | RELA | Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.52 | RELA |
Zornitza Stark gene: RELA was added gene: RELA was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RELA were set to 28600438; 29305315 Phenotypes for gene: RELA were set to Mucocutaneous ulceration, chronic, MIM# 618287; Impaired NFkB activation; reduced production of inflammatory cytokines; autoimmune cytopaenias Review for gene: RELA was set to AMBER Added comment: Two families reported, somewhat different phenotypes. Sources: Expert list |
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| Combined Immunodeficiency v0.51 | RELB | Zornitza Stark Marked gene: RELB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.51 | RELB | Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.51 | RELB | Zornitza Stark Classified gene: RELB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.51 | RELB | Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Combined Immunodeficiency v0.50 | RELB |
Zornitza Stark gene: RELB was added gene: RELB was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RELB were set to 7834753; 26385063 Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections Review for gene: RELB was set to AMBER Added comment: Single family reported, functional data. Sources: Expert list |
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| Combined Immunodeficiency v0.48 | POLD1 |
Zornitza Stark changed review comment from: Three individuals from two generations of a consanguineous family reported, some functional data. Sources: Expert list; to: Three individuals from two generations of a consanguineous family reported, some functional data. Another unrelated individual reported in PMID 31449058, more functional data. Sources: Expert list |
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| Combined Immunodeficiency v0.31 | NSMCE3 |
Zornitza Stark gene: NSMCE3 was added gene: NSMCE3 was added to Combined immunodeficiency_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: NSMCE3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSMCE3 were set to 27427983 Phenotypes for gene: NSMCE3 were set to Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241 Review for gene: NSMCE3 was set to AMBER Added comment: Two unrelated families, some functional data. Sources: Expert list |
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| Combined Immunodeficiency v0.23 | HELLS |
Zornitza Stark gene: HELLS was added gene: HELLS was added to Combined immunodeficiency_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: HELLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HELLS were set to 26216346 Phenotypes for gene: HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM#616911 Review for gene: HELLS was set to GREEN Added comment: Five individuals from four unrelated families. Sources: Expert list |
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| Combined Immunodeficiency v0.21 | GINS1 |
Zornitza Stark gene: GINS1 was added gene: GINS1 was added to Combined immunodeficiency_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: GINS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS1 were set to 28414293 Phenotypes for gene: GINS1 were set to Immunodeficiency 55, MIM#617827 Review for gene: GINS1 was set to GREEN Added comment: IUGR, natural killer (NK) cell deficiency, and chronic neutropenia;mild facial dysmorphism, dry or eczematous skin, and recurrent infections with both viruses and bacteria. At least 5 patients from four unrelated families reported. Sources: Expert list |
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| Combined Immunodeficiency v0.15 | CDCA7 |
Zornitza Stark gene: CDCA7 was added gene: CDCA7 was added to Combined immunodeficiency_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: CDCA7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CDCA7 were set to 26216346 Phenotypes for gene: CDCA7 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910 Review for gene: CDCA7 was set to GREEN Added comment: Five patients from four unrelated families; presents with recurrent infections in childhood, dysmorphic features and ID variable. Sources: Expert list |
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| Combined Immunodeficiency v0.11 | MSN |
Zornitza Stark gene: MSN was added gene: MSN was added to Combined immunodeficiency_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: MSN was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: MSN were set to 27405666 Phenotypes for gene: MSN were set to Immunodeficiency 50, MIM# 300988 Review for gene: MSN was set to GREEN Added comment: Seven males from five unrelated families reported. Sources: Expert list |
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