Work

Low Prevalence of HNF1A Mutations After Molecular Screening of Multiple MODY Genes in 58 Italian Families Recruited in the Pediatric or Adult Diabetes Clinic From a Single Italian Hospital

Year: 2014

Type: article

Abstract: Maturity-onset diabetes of the young (MODY; MIM # 606391) is a genetically and clinically heterogeneous form of di-abetes, accounting for 1–2 % of all dia-betes cases (1). MODY is characterized by mild hyperglycemia or overt diabetes usually detected in three consecutive generations, with onset before the age of 25 years and absence of type 1 diabe-tes autoantibodies. Among the thirteen MODY genes identified, two subtypes, GCK-MODY and HNF1A-MODY, account for most of cases (1). The prevalence of GCK-MODY has been reported higher in Southern Europe (2), while HNF1A-MODY is the most common MODY subtype in Northern Europe (3). This dif-ferencemight be attributable to the clin-ical setting in which genetic screening is performed, especially when pediatric and adult diabetes clinics are distinct en-tities. We addressed this issue by inves-tigating MODY patients identified in the pediatric or in the adult diabetes clinics of the same research-based hospital in Southern Italy to obtain data from a ho-mogeneous geographic and genetic background. We selected 58 probands of Italian ancestry fulfilling stringent MODY criteria: 1) blood glucose.100 mg/dL (confirmed), 2) no type 1 diabetes autoantibodies, and 3) three consecutive generations with hyperglycemia before age 25 years. Forty-three patients were recruited at the pediatric clinic (age 1–18 years) and 15 at the adult clinic (age.18 years). We screened by DNA sequencing six “classic ” MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1) (1) in both groups and INS (MODY 10) and KCNJ11 (MODY 13) genes in the pediatric group. In the pediatric group, we identified

Source: Diabetes Care

DOI: 10.2337/dc14-1788