Mutations in DENND1A gene contribute to polycystic ovary syndrome
An analysis of 62 families with cases of polycystic ovary syndrome has associated rare variants of DENND1A gene with the disease.
Whole genome sequencing covered 262 individuals, including ten with polycystic ovary syndrome.
Initial association of variants in the genome pointed to 339 genes (eg. C9orf3, HMGA2, ZBTB16, TOX3, THADA). Out of them, DENND1A was the most significantly associated gene with the syndrome.
DENND1A can possess even 32 mutations contributing to polycystic ovary syndrome. Only two mutations directly change protein sequence (coding region) and remaining 30 mutations lead to regulatory or indirect changes (non-coding region).
Computational simulations revealed that these mutations mostly affect binding of regulatory molecules, therefore disrupting proper activation of the gene. Change of DENND1A function leads to modifications of hormone production on an ovarian cells level.
As the syndrome is common and heritable, the findings are essential for the earliest possible diagnostic and therapeutic approach.
More: “Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in pathogenesis of polycystic ovary syndrome”, M. Dapas et al., 2018, doi:10.1101/460972.