Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients

•We report the impact of variants in genetic and chromosomal levels on POF using NGS.•XY karyotype with distal deletions in Y chromosome was detected in two POF patients.•Candidate causal variants in genes related with POF and sex reversal were identified.•We suggest NGS as a powerful tool to study a heterogeneous disease such as POF.

Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF.