Whole exome and targeted sequencing reveal novel mutations associated with inherited PCOS condition in an Indian cohort

Autor: Janani, Dakshina Moorthy, Ramasubramanyan, Sharada, Chellappa, Venkatesh, Santhanam, Rekha, Manickam, Ranjani, Shameli, Jeevamani, Balasundaram, Usha
Zdroj: Journal of Human Genetics; January 2023, Vol. 68 Issue: 1 p39-46, 8p
Abstrakt: A cohort of polycystic ovary syndrome (PCOS) women presents themselves with persistent abnormal reproductive hormone levels and has a familial representation of characteristics. In our study, we have aimed to identify genetic variants which are inherited across such PCOS families and also validate them among Indian population. Independent discovery was done by whole exome sequencing in a three-generation family (Family P01). Validation was done by targeted sequencing at 30,000x using HaloPlex panel in 9 families (P01-P09). The variants were filtered and reported according to American College of Medical Genetics and Genomics (ACMG) guidelines. Mutation burden analysis and in-silicofunctional analyses were performed. After careful annotation analyses, we report 24 likely pathogenic variants from 21 genes, out of which 8 are novel structural variants, 14 missense variants and 2 intronic variants. Out of these, 3 variants from the genes FSHR, SCARB1, and INSRare involved in the ovarian steroidogenesis pathway and 5 variants from genes DFFB, ACTG1, GPX4, CYC1and ALDOAdirectly or indirectly trigger the apoptotic pathways. Three ovarian steroidogenesis variants, FSHR, SCARB1 and INSRwere screened among Indian women using a case-control approach to validate these variant’s pathogenicity in Indian PCOS women. Variants of SCARB1and INSRwere found to be pathogenic to Indian PCOS women, while FSHRvariants did not show significant association to PCOS cases.
Databáze: Supplemental Index
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