Objective:  To describe a proband with features of type 2 diabetes who was found to have concomitant maturity‐onset diabetes of the young (MODY) and the consequent multigeneration genetic analysis. Design:  Familial genetic analysis. Setting:  Tertiary university medical center. Participants:  The proband was a 13.5‐yr‐old boy with marked non‐ketotic hyperglycemia, obesity, systolic hypertension, and insulin resistance. His mother, maternal aunt, grandmother, and great grandmother had diabetes; his father was obese and had early ischemic heart disease. Interventions:  Clinical examination, laboratory work‐up, and DNA study. Outcome measures:  Mutation in hepatocyte nuclear factor‐1α gene, the most common cause of MODY. Results:  The proband showed elevated C‐peptide level and was negative for beta‐cell antibodies. On genetic analysis for MODY, the 291fsinsC mutation was identified in all affected family members. A younger sister who was obese but had no signs of impaired glucose tolerance was also tested on the basis of these findings and was found to have the same mutation. Conclusions:  The patient, who presented with apparent type 2 diabetes, had concomitant MODY 3, inherited from his mother’s side, and some features of type 2 diabetes secondary to marked obesity. This combination probably caused an earlier and more severe presentation of the disease and had significant implications for medical management. A search for MODY mutations should be considered in patients with a history of diabetes in three generations of one side of the family, even those in whom the clinical picture resembles type 2 diabetes.

Maturity onset diabetes of the young (MODY) is characterized by a primary defect in insulin secretion with non-ketotic hyperglycemia, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of autoantibodies. The aim of this study was to characterize the genetic basis of MODY in different ethnic groups in the Israeli population. Fifty-nine unrelated Israeli patients with MODY were assessed for mutations in the three common MODY genes: hepatocyte nuclear factor (HNF)-4alpha, glucokinase (GCK), and transcription factor 1 (TCF1). Overall, 11 mutations in 12 unrelated families were found (20.3% of patients), for a relative frequency of 1.7% for MODY1, 8.5% for MODY2, and 10.1% for MODY3. Four mutations were novel, including the first gross deletion ever described in the TCF1 gene. The low overall mutation frequency found here may suggest the involvement of other, yet unidentified, genes in the etiology of MODY in Israel.