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| Mendeliome v1.1816 | ATXN7L3 |
Chirag Patel gene: ATXN7L3 was added gene: ATXN7L3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN7L3 were set to PMID: 38753057 Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500 Review for gene: ATXN7L3 was set to GREEN gene: ATXN7L3 was marked as current diagnostic Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities. A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51). Sources: Literature |
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| Mendeliome v1.571 | BUB1 | Zornitza Stark Phenotypes for gene: BUB1 were changed from Neurodevelopmental disorder, BUB1-related MONDO:0700092 to Primary microcephaly-30 (MCPH30), MIM#620183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.570 | BUB1 | Zornitza Stark edited their review of gene: BUB1: Changed phenotypes: primary microcephaly-30 (MCPH30), MIM#620183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.60 | BUB1 | Elena Savva Classified gene: BUB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.60 | BUB1 | Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.59 | BUB1 | Zornitza Stark reviewed gene: BUB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.59 | BUB1 | Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.59 | BUB1 | Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.56 | BUB1 | Elena Savva Classified gene: BUB1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.56 | BUB1 | Elena Savva Gene: bub1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.53 | BUB1 | Elena Savva Classified gene: BUB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.53 | BUB1 | Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.52 | BUB1 | Zornitza Stark Marked gene: BUB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.52 | BUB1 | Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.52 | BUB1 | Zornitza Stark Phenotypes for gene: BUB1 were changed from Intellectual disability and microcephaly to Neurodevelopmental disorder, BUB1-related MONDO:0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.51 | BUB1 | Zornitza Stark Classified gene: BUB1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.51 | BUB1 | Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.44 | BUB1 | Paul De Fazio edited their review of gene: BUB1: Changed phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092, Intellectual disability and microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.44 | BUB1 |
Paul De Fazio gene: BUB1 was added gene: BUB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306 Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly Review for gene: BUB1 was set to GREEN gene: BUB1 was marked as current diagnostic Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants: P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable. P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity. BUB1 patient cells have impaired mitotic fidelity. Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306) Sources: Literature |
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| Mendeliome v0.4817 | BUB1B | Zornitza Stark Marked gene: BUB1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4817 | BUB1B | Zornitza Stark Gene: bub1b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4817 | BUB1B | Zornitza Stark Phenotypes for gene: BUB1B were changed from to Mosaic variegated aneuploidy syndrome 1, MIM# 257300; Premature ovarian failure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4816 | BUB1B | Zornitza Stark Publications for gene: BUB1B were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4815 | BUB1B | Zornitza Stark Mode of inheritance for gene: BUB1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4814 | BUB1B | Zornitza Stark reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32716490, 18548531; Phenotypes: Mosaic variegated aneuploidy syndrome 1, MIM# 257300, Premature ovarian failure; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4807 | BUB1B | Eleanor Williams reviewed gene: BUB1B: Rating: ; Mode of pathogenicity: None; Publications: 32716490; Phenotypes: premature ovarian insufficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | BUB1B |
Zornitza Stark gene: BUB1B was added gene: BUB1B was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: BUB1B was set to Unknown |
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