Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity-onset diabetes of the young (MODY).

摘要: Maturity-onset diabetes of the young is a genetically heterogeneous autosomal dominant form mellitus, characterized by an early age at onset and primary defect in beta-cell function. Forty families with clinical presentation suggestive MODY were screened for most common subtypes caused mutations genes encoding glucokinase (GCK, MODY2) hepatocyte nuclear 1-alpha (HNF1A/TCF1, MODY3). Overall, 14 found (35%) giving relative frequency 22.5% 12.5% MODY2 MODY3, respectively. Five nine GCK identified novel included two deletions, nonsense, one splice site mutation. The donor mutation was shown to result aberrant transcript owing recruitment cryptic site. translated protein predicted contain frame insertion amino acids. Among five HNF1A identified, three comprising missense mutation, deletion, insertion. In addition, several polymorphisms within their allele frequencies estimated. Knowledge genetic cause has significant impact on therapeutic decision making may help identify family members risk diabetes.