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• W2015031894 abstract "To determine the distribution of the age at onset of diabetes (maturity-onset diabetes of the young-3 [MODY3]) and to identify determinants of the onset of diabetes in carriers of HNF-1alpha mutations.Extended families (n = 104) with type 2 diabetes inherited in a dominant pattern were recruited and screened for diabetes-causing mutations in HNF-1alpha.HNF-1alpha mutations cosegregated with diabetes in only 13 families, all with a mean age at onset <35 years. Insulin secretion was diminished or absent in mutation carriers (n = 101), and diabetes developed in 65% by age 25 years and in 100% by age 50 years. If the mutation was inherited from the mother, diabetes onset was very young in those exposed to diabetes in utero; 57 +/- 8% were affected by age 15 years as compared with 0.0% in those not exposed (P < 7 x 10(-6)). By age 25 years, the difference was reduced (85 +/- 6 and 55 +/- 12%, respectively; P = 0.02). If the mutation was inherited from the father, diabetes developed in 52 +/- 8% by age 25 years. Age at diagnosis was shown to be highly heritable (h(2) = 0.47, P = 0.003). When parent of origin was included in the analyses, the magnitude of genetic contribution increased markedly (h(2) = 0.91).Mutations in HNF-1alpha accounts for diabetes in a small proportion of families with a dominant pattern of inheritance. Age at onset of diabetes in MODY3 families varied widely and was influenced by familial factors (including modifying genes) and parent of origin (whether a mutation carrier was exposed to diabetes in utero)." @default.
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• W2015031894 date "2002-12-01" @default.
• W2015031894 modified "2023-09-25" @default.
• W2015031894 title "Determinants of the Development of Diabetes (Maturity-Onset Diabetes of the Young-3) in Carriers of <i>HNF-1</i>α Mutations" @default.
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• W2015031894 doi "https://doi.org/10.2337/diacare.25.12.2292" @default.
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