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| Fetal anomalies v1.129 | STX5 |
Ain Roesley gene: STX5 was added gene: STX5 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STX5 were set to 34711829 Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related Review for gene: STX5 was set to AMBER gene: STX5 was marked as current diagnostic Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US). Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start) phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol. Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking Sources: Literature |
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| Fetal anomalies v0.4692 | NUP85 |
Zornitza Stark gene: NUP85 was added gene: NUP85 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP85 were set to 34170319 Phenotypes for gene: NUP85 were set to Microcephaly, MONDO:0001149, NUP85-related Review for gene: NUP85 was set to AMBER Added comment: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle. Variants in this gene are also associated with nephrotic syndrome. Sources: Expert Review |
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| Fetal anomalies v0.3879 | STAR | Zornitza Stark Marked gene: STAR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3879 | STAR | Zornitza Stark Gene: star has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3879 | STAR | Zornitza Stark Phenotypes for gene: STAR were changed from CHOLESTEROL DESMOLASE-DEFICIENT CONGENITAL ADRENAL HYPERPLASIA to Lipoid adrenal hyperplasia (MIM#201710) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3878 | STAR | Zornitza Stark Publications for gene: STAR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3877 | STAR | Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3877 | STAR | Daniel Flanagan reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8948562, 16968793; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3869 | STAR | Belinda Chong reviewed gene: STAR: Rating: RED; Mode of pathogenicity: None; Publications: 7892608, 8948562, 9097960, 11061515, 11297612, 14764819, 16968793, 9326645; Phenotypes: Lipoid adrenal hyperplasia MIM#201710; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3587 | MYH3 | Alison Yeung Phenotypes for gene: MYH3 were changed from DISTAL ARTHROGRYPOSIS TYPE 2A; DISTAL ARTHROGRYPOSIS TYPE 2B to Arthrogryposis, distal, type 2A (Freeman-Sheldon) MIM# 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) MIM# 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, MIM#178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, MIM# 618469 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2756 | ERGIC1 |
Krithika Murali gene: ERGIC1 was added gene: ERGIC1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERGIC1 were set to 28317099; 34037256; 31230720 Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100 Review for gene: ERGIC1 was set to GREEN Added comment: Recent Panelapp review by Z. Stark Oct 2021 - no new publications since --- Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed. Created: 14 Oct 2021, 7:23 a.m. | Last Modified: 14 Oct 2021, 7:23 a.m. Panel Version: 0.9373 Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Sources: Literature Sources: Literature |
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| Fetal anomalies v0.1526 | FAM58A | Zornitza Stark Phenotypes for gene: FAM58A were changed from STAR SYNDROME to STAR syndrome MIM#300707 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | FAM58A | Belinda Chong reviewed gene: FAM58A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18297069, 8818947, 28225384; Phenotypes: STAR syndrome MIM#300707; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.774 | ELOVL4 |
Belinda Chong changed review comment from: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects; to: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects |
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| Fetal anomalies v0.774 | ELOVL4 | Belinda Chong reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24566826, 26258735, 30065956, 22100072, 24571530, 33652762, 10634627, 8002834; Phenotypes: Ichthyosis, spastic quadriplegia, and mental retardation MIM#614457, Spinocerebellar ataxia 34 MIM#133190, Stargardt disease 3 MIM#600110; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.610 | CRLF1 |
Zornitza Stark edited their review of gene: CRLF1: Added comment: Micrognathia, camptodactyly are features. Crisponi/cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis. Multiple unrelated families reported.; Changed rating: GREEN; Changed publications: 12509788, 17436251, 17436252 |
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| Fetal anomalies v0.0 | STAR |
Zornitza Stark gene: STAR was added gene: STAR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STAR were set to CHOLESTEROL DESMOLASE-DEFICIENT CONGENITAL ADRENAL HYPERPLASIA |
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| Fetal anomalies v0.0 | FAM58A |
Zornitza Stark gene: FAM58A was added gene: FAM58A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: FAM58A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: FAM58A were set to STAR SYNDROME |
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