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| Mendeliome v1.2737 | BCORL1 |
Zornitza Stark edited their review of gene: BCORL1: Added comment: Association with spermatogenic failure: i) PMID: 38342987- novel hemizygous nonsense variant (c.1564G > T:p.Glu522*) in a male patient with oligoasthenoteratozoospermia (OAT) from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Also identified four hemizygous missense variants (c.2615T > G:p.Val872Gly, c.2669G > A:p.Arg890Gln, c.3164A > G:p.Asp1055Gly and c.3344C > T:p.Pro1115Leu) in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%). They hypothesized that the BCORL1 (c.2615 T > G, c.2669G > A, c.3164A > G, c.3344C > T) missense mutations may have led to an accumulation of dysfunctional toxic proteins that resulted in a more severe male infertility phenotype in the patient (NOA). ii) PMID: 32376790- Hemizygous missense variant in a male patient with NOA without other diseases, which also found that the knockout of Bcorl1 in mice resulted in OAT with the abnormal brain development. It had not been previously linked to male infertility. This study demonstrates, for the first time, that loss of Bcorl1 causes spermatogenesis failure. iii) PMID: 39267058- hemizygous missense variant (p.Arg19Gln) in a infertile male with oliogasthenozoospermia, no functional data iv) PMID: 39189935- novel hemizygous missense variant (p.G1391R) and a recurrent variant (p.V872G) in BCORL1 from four OAT patients. Functional assays showed that the variants disturb the transcription of spermatogenetic genes such as SYCE1 and DAZL, impair the interaction with HDAC7, and cause epigenetic changes such as changes in level of histone modification with different extent, including the enhancement in acetylation of H3K14, and the reduction in acetylation of H4K5 and H4K8.; Changed rating: GREEN; Changed publications: 24123876, 30941876, 38342987, 32376790, 39267058, 39189935; Changed phenotypes: Shukla-Vernon syndrome, MIM#301029, Spermatogenic failure, MONDO:0004983, BCORL1-related |
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| Mendeliome v1.1237 | DAZL | Zornitza Stark Phenotypes for gene: DAZL were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DAZL-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9918 | DAZL | Bryony Thompson Marked gene: DAZL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9918 | DAZL | Bryony Thompson Gene: dazl has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9918 | DAZL | Bryony Thompson Classified gene: DAZL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9918 | DAZL | Bryony Thompson Gene: dazl has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9917 | DAZL |
Bryony Thompson gene: DAZL was added gene: DAZL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DAZL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DAZL were set to 34794894; 33095795; 16884537; 9288969 Phenotypes for gene: DAZL were set to Primary ovarian insufficiency Review for gene: DAZL was set to AMBER Added comment: PMID: 33095795 - Single POI case with heterozygous stopgain (c.640C>T:p.Q214*). PMID: 16884537 - 4 heterozygous unrelated early menopause/POI cases with heterozygous missense (all rare in gnomAD v2.1, except p.Asn10His which has 14 hets) PMID: 9288969 - supporting knockout mouse model Sources: Literature |
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