Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency

Objective To investigate whether gene variants of SOHLH1 exist in Chinese and Serbian patients with primary ovarian insufficiency (POI). Design Case-control genetic study. Setting University hospitals. Patient(s) A total of 364 Han Chinese and 197 Serbian women with nonsyndromic POI and ethnically matched controls. Intervention(s) None. Main Outcome Measure(s) SOHLH1 gene sequencing. Result(s) We found 10 novel heterozygous variants in our cohorts of 561 women with POI but none in the 600 ethnically matched controls. Statistical and bioinformatic analyses indicated that three of the eight variants in Chinese POI cases are potentially disease causing. They comprise two missense variants (p.Ser317Phe and p.Glu376Lys) that might each change activity of the SOHLH1 protein as a transcription factor and one variant (c.*118C>T) located in the 3′ untranslated region of the SOHLH1 gene, which might generate a new binding site for the microRNA hsa-miR-888-5p. Of the two variants in the Serbian POI cases, both were synonymous, and no missense variant was identified. The allele frequencies of some known single-nucleotide polymorphisms were statistically significantly different between patients and controls in both the Chinese and Serbian groups. Conclusion(s) Our results suggest that SOHLH1 may be regarded as a new candidate gene for POI.