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| Mendeliome v1.2430 | CCNB3 |
Zornitza Stark gene: CCNB3 was added gene: CCNB3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CCNB3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCNB3 were set to 35722368; 32938693; 34021051; 30770433; 34850816 Phenotypes for gene: CCNB3 were set to Recurrent pregnancy loss, susceptibility to, MONDO:0000144, CCNB3-related Review for gene: CCNB3 was set to GREEN Added comment: i) PMID: 35722368- homozygous missense variant (p.P119Q) in the female of unexplained recurrent pregnancy loss (RPL) couple (couple 29) ii) PMID: 32938693- homozygous missense variant (p.V1251D) in two sisters with RPL and two of their POCs were characterised and found to be triploid digynic due to the failure of meiosis II. iii) PMID: 34021051- novel homozygous frameshift variant (p.Val1321Glyfs*4, due to splicing causing exon skipping) in a patient with 16 RPL and one of her miscarriages is triploid digynic resulted from the failure of meiosis I. Supporting mouse evidence: iv) PMID: 30770433- Ccnb3 knockout also causes female infertility due to the failure of metaphase to anaphase transition in meiosis I and the extrusion of the first polar body. The infertility in these mice appeared to be due to embryonic lethality before embryonic day 7.5 and some of their oocytes fertilised by intracytoplasmic sperm injection led to triploid embryos. v) PMID: 34850816- Ccnb3-deficient mouse model is similar to a human infertility condition—recurrent pregnancy loss (RPL). Their findings demonstrate that the triploidy of embryos derived from Ccnb3-deficient oocytes is the primary cause of embryo death (i.e., such embryos can be rescued with euploid nuclei, whereas cytoplasmic Ccnb3 transcript is dispensable for zygotic genome activation and embryo development). Sources: Expert Review |
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| Mendeliome v1.1992 | RFC4 |
Chirag Patel gene: RFC4 was added gene: RFC4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RFC4 were set to PMID: 39106866 Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder Review for gene: RFC4 was set to GREEN gene: RFC4 was marked as current diagnostic Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9). WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease. The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown. Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression. Sources: Literature |
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| Mendeliome v0.7598 | SPEN | Zornitza Stark Marked gene: SPEN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7598 | SPEN | Zornitza Stark Gene: spen has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7598 | SPEN | Zornitza Stark Phenotypes for gene: SPEN were changed from Intellectual disability; autism; congenital anomalies to Radio-Tartaglia syndrome, MIM# 619312; Intellectual disability; autism; congenital anomalies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7597 | SPEN | Zornitza Stark Publications for gene: SPEN were set to 33057194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7596 | SPEN | Zornitza Stark reviewed gene: SPEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Radio-Tartaglia syndrome, MIM# 619312; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6508 | SPEN | Zornitza Stark Phenotypes for gene: SPEN were changed from Developmental disorders to Intellectual disability; autism; congenital anomalies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6501 | SPEN | Alison Yeung Classified gene: SPEN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6501 | SPEN | Alison Yeung Gene: spen has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6495 | SPEN | Chern Lim reviewed gene: SPEN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33596411; Phenotypes: Developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5303 | SPEN | Bryony Thompson Marked gene: SPEN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5303 | SPEN | Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5303 | SPEN | Bryony Thompson Classified gene: SPEN as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5303 | SPEN | Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5302 | SPEN |
Bryony Thompson gene: SPEN was added gene: SPEN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPEN were set to 33057194 Phenotypes for gene: SPEN were set to Developmental disorders Review for gene: SPEN was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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