Hattersley A T, Turner R C, Permutt M A, Patel P, Tanizawa Y, Chiu K C, O'Rahilly S, Watkins P J, Wainscoat J S
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, UK.
Lancet. 1992 May 30;339(8805):1307-10. doi: 10.1016/0140-6736(92)91958-b.
Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes that presents from the second decade and has an autosomal dominant mode of inheritance. We have investigated the glucokinase gene, a candidate gene for diabetes, in two MODY pedigrees. In a large 5-generation pedigree (BX) with 15 diabetic members, use of a microsatellite polymorphism revealed linkage of diabetes to the glucokinase locus on chromosome 7p. A peak lod score of 4.60 was obtained at a recombination fraction (theta) of zero. This finding suggests that a defective glucokinase gene contributes to the diabetes phenotype in this pedigree. This is not universal in MODY since linkage to the glucokinase locus was excluded in a second pedigree M (lod score = -7.36 at theta = 0). The affected members in pedigree BX were diagnosed either when young (in pregnancy or on screening) or when they presented symptomatically in middle and old age; most of them were treated by diet alone. Defects in the glucokinase gene may play an important part in the pathogenesis of type 2 diabetes.
青年发病的成年型糖尿病（MODY）是2型糖尿病的一种亚型，始于第二个十年，具有常染色体显性遗传模式。我们在两个MODY家系中研究了作为糖尿病候选基因的葡萄糖激酶基因。在一个有15名糖尿病成员的大型5代家系（BX）中，使用微卫星多态性揭示了糖尿病与7号染色体短臂上葡萄糖激酶基因座的连锁关系。在重组率（θ）为零时获得了4.60的最高对数优势比分。这一发现表明，有缺陷的葡萄糖激酶基因导致了该家系中的糖尿病表型。这在MODY中并不普遍，因为在第二个家系M中排除了与葡萄糖激酶基因座的连锁关系（在θ = 0时对数优势比分=-7.36）。家系BX中的患病成员要么在年轻时（孕期或筛查时）被诊断出来，要么在中老年出现症状时被诊断出来；他们大多数仅通过饮食治疗。葡萄糖激酶基因缺陷可能在2型糖尿病的发病机制中起重要作用。
