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| Infertility and Recurrent Pregnancy Loss v0.103 | MTHFR |
Jasmine Chew gene: MTHFR was added gene: MTHFR was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: MTHFR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MTHFR were set to 37260775; 39534907; 38322638 Phenotypes for gene: MTHFR were set to Recurrent pregnancy loss susceptibility Review for gene: MTHFR was set to AMBER Added comment: PMID: 37260775- RPL5 couple was found to be carriers for mutation in the MTHFR gene. It is already known that women with a MTHFR variant have a higher risk for pregnancy-related issues such as miscarriages, preeclampsia, or a baby born with birth defects, such as spina bifida. The theory behind the connection between the MTHFR mutation and pregnancy loss is that tiny blood clots are formed because of homocysteinemia, which blocks the flow of nutrition to the placenta, essentially starving the fetus and triggering a spontaneous abortion (Dell’dera et al., 2018- PMID: 29435277). ii) PMID: 39534907- The MTHFR C677T variant showed strong associations with unexplained RPL, particularly the CT genotype (OR: 6.07, 95% CI: 3.00-12.93; p < 0.001) and TT genotype (OR: 14.62, 95% CI: 2.85-114.77; p = 0.003) in Vietnamese population. iii) PMID: 38322638- 6.2% of couples with a history of RPL had MTHFR C677T in an Iranian population Note: MTHFR is a thrombophilic marker and DNA methylation- PMID: 34745108). Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | BLM |
Jasmine Chew gene: BLM was added gene: BLM was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLM were set to 34794894; 29056561; 28846287 Phenotypes for gene: BLM were set to Bloom syndrome, MIM# 210900 Review for gene: BLM was set to GREEN Added comment: PMID: 28846287 (Gene Review)- Women may be fertile but often have early menopause, and men tend to be infertile. Most men with BSyn assessed for infertility have had azoospermia or severe oligospermia. PMID: 35671666, PMID: 24858046- BLM physically interacts with MUS81, an endonuclease involved in the restart of stalled replication forks and HR repair. Loss of Mus81 in Blm hypomorph mutant mice leads to infertility, and growth and developmental defects that are not observed in single mutants. Double mutant cells and mice were hypersensitive to Mitomycin C and γ-irradiation (IR) compared with controls and their repair of DNA double-strand breaks (DSBs) mediated by HR pathway was significantly defective, whereas their non-homologous-end-joining repair was elevated compared with controls. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | NUP107 |
Jasmine Chew changed review comment from: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158 - Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature; to: FeRGI database- moderate evidence for ovarian dysgenesis- PMID: 26485283; 34707299; 29363275 (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158 - Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | NUP107 |
Jasmine Chew changed review comment from: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158- Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature; to: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158 - Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | NUP107 |
Jasmine Chew changed review comment from: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158- Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature; to: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158- Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | NUP107 |
Jasmine Chew changed review comment from: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158-Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature; to: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158- Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | NUP107 |
Jasmine Chew gene: NUP107 was added gene: NUP107 was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP107 were set to 26485283; 34707299; 29363275 Phenotypes for gene: NUP107 were set to Ovarian dysgenesis 6, MIM# 618078 Review for gene: NUP107 was set to GREEN Added comment: FeRGI database- moderate evidence for ovarian dysgenesis (biallelic variants reported for ovarian dysgenesis/premature ovarian insufficiency) https://mednexus.org/doi/full/10.4103/2096-2924.268158-Knockdown of NUP107 expression had little effect on the growth and number of human granulosa cell (GC). Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone (FSH) by decreasing the expression of estrogen synthesis-related genes AR, CYP17A1, CYP19A1, STAR, and NR5A1. Moreover, knockdown of NUP107 decreased the expression of AMHR2, FSHR, LHR, and ESR1 in GCs, but had no effect on the expression of ESR2. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.103 | LHX8 |
Jasmine Chew gene: LHX8 was added gene: LHX8 was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: LHX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LHX8 were set to 27603904; 34095689; 29329412; 36029299 Phenotypes for gene: LHX8 were set to Inherited premature ovarian failure, MONDO:0019852, LHX8-related Review for gene: LHX8 was set to GREEN Added comment: PMID:27603904; 34095689- reported POI patient with the same heterozygous missense p.Ala325Val variant. PMID: 29329412 - Lhx8 knockout mouse model demonstrates that Lhx8-/- ovaries maintain the same number of germ cells throughout embryonic development; rapid decrease in the pool of oocytes starts shortly before birth. Lhx8-/- oocytes failed to repair DNA damage-which normally occurs when meiosis is initiated during embryonic development and DNA damage repair genes were downregulated throughout the oocyte short lifespan. PMID: 36029299- 5 heterozygous loss-of-function LHX8 variants were identified from 6 independent families with infertility characterized by oocyte maturation arrest. All the identified variants in LHX8 produced truncated LHX8 protein and resulted in loss of LHX8 nuclear localization in both HeLa cells and mouse oocytes. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.84 | STAR | Zornitza Stark Marked gene: STAR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.84 | STAR | Zornitza Stark Gene: star has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.84 | STAR | Zornitza Stark Classified gene: STAR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.84 | STAR | Zornitza Stark Gene: star has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.83 | STAR | Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | STAR |
Jasmine Chew changed review comment from: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients: i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro. ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins. Sources: Literature; to: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients: i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro. ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, of the wild-type protein activity, respectively. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.63 | STAR |
Jasmine Chew gene: STAR was added gene: STAR was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAR were set to 38913505; 36733346 Phenotypes for gene: STAR were set to Lipoid adrenal hyperplasia, MIM# 201710 Review for gene: STAR was set to GREEN Added comment: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients: i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro. ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins. Sources: Literature |
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