Frayling T M, Bulamn M P, Ellard S, Appleton M, Dronsfield M J, Mackie A D, Baird J D, Kaisaki P J, Yamagata K, Bell G I, Bain S C, Hattersley A T
Institute of Clinical Science, University of Exeter, Devon, U.K.
Diabetes. 1997 Apr;46(4):720-5. doi: 10.2337/diab.46.4.720.
Mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene have recently been shown to cause maturity-onset diabetes of the young (MODY). We have examined 15 U.K. MODY families for mutations in the coding region of the HNF-1alpha gene. Eight different mutations, three frameshift (P291fsinsC, P379fsdelCT, and A443fsdelCA) and five missense mutations (P129T, R131W, R159W, P519L, and T620I), were identified in eleven families (73%). The previously reported mutation P291fsinsC was found in four pedigrees. A screen of a further 32 probands with early onset (<40 years of age) NIDDM showed the mutation in two additional families. This common mutation was present on at least three different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than a founder effect. We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. Mutation-based genetic counseling can now be considered for the majority of patients with MODY.
最近研究表明，肝细胞核因子-1α（HNF1α）基因的突变可导致青年发病的成年型糖尿病（MODY）。我们对15个英国家庭的MODY患者进行了HNF-1α基因编码区突变检测。在11个家庭（73%）中发现了8种不同的突变，其中3种为移码突变（P291fsinsC、P379fsdelCT和A443fsdelCA），5种为错义突变（P129T、R131W、R159W、P519L和T620I）。在4个家系中发现了先前报道的P291fsinsC突变。对另外32例早发（<40岁）非胰岛素依赖型糖尿病（NIDDM）先证者进行筛查，又在另外2个家庭中发现了该突变。这种常见突变至少存在于3种不同的单倍型上，提示其高频率是由于反复突变而非奠基者效应。我们证明，HNF-1α基因的突变是英国家庭中MODY的常见病因，可导致早发NIDDM，并伴有进行性临床病程。现在，对于大多数MODY患者可考虑进行基于突变的遗传咨询。
