HNF1α mutations are present in half of clinically defined MODY patients in South-Brazilian individuals

Abstract

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Heterozygous mutations in at least seven genes can cause MODY. In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1alpha (hepatocyte nuclear factor 1alpha) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. Heterozygous variants in GCK and HNF1alpha genes were observed respectively in one (7.7%), and six (46.2%) families. The six HNF1alpha variants are likely to cause diabetes in the families where they were observed. However, we could not ascertain whether the GCK Gly117Ser variant found in one family is a causal mutation. In conclusion, we have confirmed in a South-Brazilian population that HNF1alpha mutations are a common cause of monogenic diabetes in adults selected with strict clinical diagnostic criteria.