Tack C J, Hattersley A T
Afd. Algemene Interne Geneeskunde, Academisch Ziekenhuis St. Radboud, Nijmegen.
Ned Tijdschr Geneeskd. 1998 Oct 10;142(41):2252-6.
To study the molecular genetic basis of an autosomal dominant form of diabetes mellitus in a Dutch family.
Descriptive.
Academic Hospital Nijmegen, the Netherlands and Laboratories for Molecular Genetics, Birmingham and Exeter, Great Britain.
A large pedigree with maturity-onset diabetes of the young (MODY) was studied by taking a history and by performing laboratory analysis; DNA was isolated from peripheral blood lymphocytes and linkage analysis was carried out using genetic markers near known MODY loci. As linkage to the MODY3 gene (encoding for the transcription factor hepatocyte nuclear factor (HNF)1 alpha) was suggested, all exons of the gene were sequenced for mutation detection.
Of the 27 family members 13 were affected by diabetes. Diabetes was diagnosed at a mean age of 36.7 years, with four family members diagnosed before the age of 25. Nearly all patients were treated with diet/oral antidiabetics. Diabetic family members had lower fasting (specific) insulin concentrations than normoglycaemic family members (53.8 (SD: 5.4) versus 90.4 (SD: 12.9) pmol/l; p < 0.05). Linkage to the MODY3 gene was established. Further investigation showed a mutation in exon 2 of the gene.
This Dutch family suffered from an autosomal form of diabetes mellitus caused by a mutation in the HNFI alpha gene (MODY3). Phenotypically, the diabetes appeared to be relatively mild; it was characterised by impaired insulin secretion.
研究一个荷兰家庭中常染色体显性遗传型糖尿病的分子遗传基础。
描述性研究。
荷兰奈梅亨学术医院以及英国伯明翰和埃克塞特的分子遗传学实验室。
通过病史采集和实验室分析对一个患有青年发病型成年糖尿病（MODY）的大家系进行研究；从外周血淋巴细胞中分离DNA，并使用已知MODY基因座附近的遗传标记进行连锁分析。由于提示与MODY3基因（编码转录因子肝细胞核因子（HNF）1α）连锁，对该基因的所有外显子进行测序以检测突变。
27名家庭成员中有13人患糖尿病。糖尿病诊断时的平均年龄为36.7岁，4名家庭成员在25岁之前被诊断出。几乎所有患者都接受饮食/口服降糖药治疗。糖尿病家庭成员的空腹（特异性）胰岛素浓度低于血糖正常的家庭成员（53.8（标准差：5.4）对90.4（标准差：12.9）pmol/l；p<0.05）。确定与MODY3基因连锁。进一步研究显示该基因外显子2存在突变。
这个荷兰家庭患有一种由HNF1α基因（MODY3）突变引起的常染色体显性遗传型糖尿病。从表型上看，这种糖尿病似乎相对较轻；其特征是胰岛素分泌受损。
