Homozygous Variants in Cause Premature Ovarian Insufficiency

Overview

Journal J Med Genet

Specialty Genetics

Date 2020 Apr 19

PMID 32303603

Citations 11

Authors

Wen-Bin He

Chen Tan

Ya-Xin Zhang

Lan-Lan Meng

Fei Gong

Guang-Xiu Lu

Ge Lin

Juan Du

Yue-Qiu Tan

Affiliations

Soon will be listed here.

Abstract

Background: The genetic causes of the majority of cases of female infertility caused by premature ovarian insufficiency (POI) are unknown.

Objective: To identify the genetic causes of POI in 110 patients.

Methods: Whole-exome sequencing was performed on 110 patients with POI, and putative disease-causative variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed for functional characterisation of the identified candidate disease-causative variants.

Results: We identified two homozygous variants (NM_001040274: c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in in two patients, which had co-segregated with POI in these families. Bioinformatic analysis predicted that the two variants are deleterious, and in vitro functional analysis showed that mutant SYCP2L proteins exhibited mislocalisation and loss of function.

Conclusions: is a novel gene found to be responsible for human POI. Our findings provide a potential molecular marker for POI and improve the understanding of the genetic basis of female infertility.

Citing Articles

Premature ovarian insufficiency.

Touraine P, Chabbert-Buffet N, Plu-Bureau G, Duranteau L, Sinclair A, Tucker E Nat Rev Dis Primers. 2024; 10(1):63.

PMID: 39266563 DOI: 10.1038/s41572-024-00547-5.

Novel Loss-of-Function Variants in Infertile Males Upgrade the Gene-Disease Clinical Validity Classification for and Male Infertility to Strong.

Li J, Schilit S, Liang S, Qin N, Teng X, Zhang J Genes (Basel). 2024; 15(8).

PMID: 39202451 PMC: 11353295. DOI: 10.3390/genes15081092.

A Human Homozygous Missense Variant Does Not Cause Premature Ovarian Insufficiency in a Mouse Model.

Bakhshalizadeh S, Bird A, Sreenivasan R, Bell K, Robevska G, van den Bergen J Genes (Basel). 2024; 15(3).

PMID: 38540391 PMC: 10970702. DOI: 10.3390/genes15030333.

Bi-allelic variants in cause male infertility with asthenoteratozoospermia in humans and mice.

Meng G, Wang Y, Luo C, Tan Y, Li Y, Tan C Hum Reprod Open. 2024; 2024(1):hoae003.

PMID: 38312775 PMC: 10834362. DOI: 10.1093/hropen/hoae003.

Mechanisms of ovarian aging in women: a review.

Wang X, Wang L, Xiang W J Ovarian Res. 2023; 16(1):67.

PMID: 37024976 PMC: 10080932. DOI: 10.1186/s13048-023-01151-z.

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