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 SYCP2L 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 SYCP2L 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.
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W-BH and CT contributed equally.
Y-QT and JD jointly supervised this work.
Contributors Y-QT, JD designed the research; W-BH analysed the data and wrote the paper; W-BH, Y-XZ, L-LM and CT performed the research; FG, G-XL and GL performed the clinical work.
Funding This study was supported by grants from the National Natural Science Foundation of China (81771645 and 81971447), Hunan Provincial Natural Science Foundation of China (2019JJ51006), the Key Grant of Prevention and Treatment of Birth Defect from Hunan Province (2019SK1012), and the Research Grant of CITIC-Xiangya (YNXM-201912).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the Ethics Committee of the Reproductive and Genetic Hospital of CITIC-Xiangya of Central South University.
Provenance and peer review Not commissioned; externally peer reviewed.
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