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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.314 | TUFM |
Ain Roesley gene: TUFM was added gene: TUFM was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: TUFM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUFM were set to 37468454 Phenotypes for gene: TUFM were set to Inherited primary ovarian failure MONDO:0019852, TUFM-related Review for gene: TUFM was set to RED gene: TUFM was marked as current diagnostic Added comment: 1 family with 1 homozygote with NM_172745.3:c.524G>C: p.Gly175Ala) in vitro functional: reduction in protein expression, decreased mitochondrial membrane potential and increased reactive oxygen species production, inhibits OXPHOS activity and results in impaired autophagy activation mouse models recapitulates phenotype Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.302 | CCDC155 |
Melanie Marty gene: CCDC155 was added gene: CCDC155 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281 Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related Review for gene: CCDC155 was set to GREEN Added comment: Current HGNC name is KASH5 Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype. PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis. PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes. PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155 PMID: 35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency. Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.281 | PRDM9 |
Chirag Patel gene: PRDM9 was added gene: PRDM9 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: PRDM9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRDM9 were set to PMID: 34257419 Phenotypes for gene: PRDM9 were set to Premature ovarian insufficiency, no OMIM # Review for gene: PRDM9 was set to GREEN Added comment: The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. PRDM9 is a meiosis-specific histone H3 methyltransferase and a major determinant of meiotic recombination hotspots in mammals. 3 pathogenic heterozygous variants in PRDM9 identified in 4 patients with POI. Functional studies showed the variants in PRDM9 impaired its methyltransferase activity. Prdm9+/- mice were subfertile, and showed increased percentage of germ cells at abnormal pachytene stage with decreased number of PRDM9-dependent DSBs and insufficient recombination. Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.247 | FANCA |
Bryony Thompson changed review comment from: PMID: 33025164 - a mouse model heterozygous for a hypomorphic variant (c.3581del9, p.QEA1194-1196del) had impaired follicle development and sub-fertility. PMID: 32962729 - a POI case heterozygous for a rare missense variant (p.H780Q) PMID: 31535215 - 2 unrelated Chinese POI cases with 2 different rare missense variants (p.R591Q, 42 hets in gnomAD v2.1 & p.E1296G), both with supporting in vitro functional assays. Also, a heterozygous loss of function (Fanca+/-) mouse model showed reduced fertility and declined numbers of follicles with aging PMID: 10915769 - female knockout mice demonstrate hypogonadism and infertility Sources: Literature; to: PMID: 33025164 - a mouse model heterozygous for a hypomorphic variant (c.3581del9, p.QEA1194-1196del) had impaired follicle development and sub-fertility. PMID: 32962729 - a POI case heterozygous for a rare missense variant (p.H780Q) PMID: 31535215 - 2 unrelated Chinese POI cases with 2 different rare missense variants (p.R591Q, 42 hets in gnomAD v2.1 & p.E1296G), both with supporting in vitro functional assays. Also, a heterozygous loss of function (Fanca+/-) mouse model showed reduced fertility and declined numbers of follicles with aging PMID: 10915769 - female knockout mice demonstrate hypogonadism and infertility Hypergonadotropic hypogonadism is listed as an endocrine feature of the Fanconi anaemia phenotype in OMIM. Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.246 | FANCA |
Bryony Thompson gene: FANCA was added gene: FANCA was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: FANCA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FANCA were set to 34794894; 33025164; 31535215; 10915769 Phenotypes for gene: FANCA were set to Primary ovarian insufficiency Review for gene: FANCA was set to AMBER Added comment: PMID: 33025164 - a mouse model heterozygous for a hypomorphic variant (c.3581del9, p.QEA1194-1196del) had impaired follicle development and sub-fertility. PMID: 32962729 - a POI case heterozygous for a rare missense variant (p.H780Q) PMID: 31535215 - 2 unrelated Chinese POI cases with 2 different rare missense variants (p.R591Q, 42 hets in gnomAD v2.1 & p.E1296G), both with supporting in vitro functional assays. Also, a heterozygous loss of function (Fanca+/-) mouse model showed reduced fertility and declined numbers of follicles with aging PMID: 10915769 - female knockout mice demonstrate hypogonadism and infertility Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.231 | INSL3 |
Bryony Thompson gene: INSL3 was added gene: INSL3 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: INSL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INSL3 were set to 34794894; 33095795; 10391220; 30204868 Phenotypes for gene: INSL3 were set to Primary ovarian insufficiency Review for gene: INSL3 was set to AMBER Added comment: A single case with POI with a homozygous missense variant (p.Val18Met, 3 homozygotes in gnomAD v2.1). Additionally, female null mouse have impaired fertility associated with deregulation of the oestrous cycle Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.202 | POLR2C |
Bryony Thompson gene: POLR2C was added gene: POLR2C was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR2C were set to 34794894; 29367954 Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency Review for gene: POLR2C was set to AMBER Added comment: One family with POI segregating a nonsense variant (p.Lys152Ter) and a case with sporadic POI with a splice region variant (c.206-3C>T). Knockdown of the gene in an embryonic carcinoma cell line resulted in decreased protein production and impaired cell proliferation. Two missense in premature ovarian failure cases submitted to ClinVar by Shandong Provincial Hospital Affiliated to Shandong University (SCV001877131.1, SCV001877153.1). Sources: Literature |
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| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.159 | AIRE | Zornitza Stark Marked gene: AIRE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.159 | AIRE | Zornitza Stark Gene: aire has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.159 | AIRE | Zornitza Stark Phenotypes for gene: AIRE were changed from Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, MIM# 240300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.158 | AIRE | Zornitza Stark Mode of pathogenicity for gene: AIRE was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.157 | AIRE | Zornitza Stark Mode of inheritance for gene: AIRE was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.156 | AIRE | Zornitza Stark changed review comment from: Hypogonadism is a feature.; to: Hypogonadism is a feature. Multiple families with bi-allelic variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.156 | AIRE | Zornitza Stark edited their review of gene: AIRE: Changed publications: 16965330, 19758376, 19807739 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.156 | AIRE | Zornitza Stark reviewed gene: AIRE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, MIM# 240300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.56 | AIRE | Bryony Thompson Phenotypes for gene: AIRE were changed from to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.55 | AIRE | Bryony Thompson Mode of inheritance for gene: AIRE was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 | AIRE |
Bryony Thompson gene: AIRE was added gene: AIRE was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: AIRE was set to |
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