OBJECTIVE: This study aims to screen for genetic variants associated with premature ovarian insufficiency (POI) in a Chinese Miao pedigree. METHODS: The proband underwent whole exome sequencing (WES), and the extracted data were subjected to bioinformatics analysis using the Rare Disease Data Center (RDDC) splicing tool to identify potential genetic causes in the lineage. Sanger sequencing was employed to confirm the variants in the family, and minigene assays were used to analyze how the FIGLA variant affects pre-mRNA splicing. RESULTS: A novel heterozygous intronic and POI-associated variant in the FIGLA gene (c.385-9G>A) was identified. Splice prediction analysis showed that this variant may disrupt splicing patterns. This result was supported by the outcome of minigene assays, which revealed that the variant led to aberrant splicing of FIGLA introns. As a result, retention of a 7-bp intronic sequence from intron 2 was found in the mature mRNA. CONCLUSION: The FIGLA variant (c.385-9G>A) disrupts mRNA splicing in cells and may contribute to POI in this pedigree. Therefore, our results expand the variant spectrum of the FIGLA gene, provide valuable insights into the pathogenesis of POI for genetic counseling, and may assist clinicians in the early diagnosis of women with infertility.
Zhang et al. (Wed,) studied this question.