Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

ABSTRACT: Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 × 10^-4). We find similar results in non-Finnish European (n = 348, odds ratio = 43, P = 5 × 10^-5) and Finnish (n = 80, odds ratio = 22, P = 1 × 10^-6) replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to

SUBMITTER: Patel KA 

PROVIDER: S-EPMC5638866 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature