基因中的纯合变异会导致卵巢早衰。
Homozygous variants in cause premature ovarian insufficiency.
机构信息
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, Hunan, China.
Reproductive and Genetic Hospital CITIC Xiangya, Changsha 410078, Hunan, China.
出版信息
J Med Genet. 2021 Mar;58(3):168-172. doi: 10.1136/jmedgenet-2019-106789. Epub 2020 Apr 17.
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.
背景
大多数由卵巢早衰（POI）引起的女性不孕病例的遗传原因尚不清楚。
目的
确定 110 例 POI 患者的遗传原因。
方法
对 110 例 POI 患者进行全外显子组测序，并通过 Sanger 测序验证疑似致病变异。对鉴定出的候选致病变异进行生物信息学和体外功能分析，以对其功能特征进行功能表征。
结果
我们在两名患者中发现了两个纯合变异（NM_001040274：c.150_151del（p.Ser52Profs*7），c.999A>G（p.Ile333Met）），这些变异在这些家族中与 POI 共分离。生物信息学分析预测这两种变异是有害的，体外功能分析表明突变的 SYCP2L 蛋白发生了定位错误和功能丧失。
结论
是一个新发现的与人类 POI 相关的基因。我们的发现为 POI 提供了一个潜在的分子标志物，并提高了对女性不孕遗传基础的理解。
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