Anikster Y, Shaag A, Joseph A, Mandel H, Ben-Zeev B, Christensen E, Elpeleg O N
Metabolic Disease Unit, Shaare-Zedek Medical Center, Jerusalem.
Am J Hum Genet. 1996 Nov;59(5):1012-8.
Mutation analysis was performed in eight families (16 patients) with glutaric aciduria type I (GA-I), which were all the families diagnosed in Israel in the years 1987-1994. Six families were of Moslem origin and two were non-Ashkenazi Jews. The entire coding region of the cDNA of the glutaryl-CoA dehydrogenase gene was sequenced in one patient of each family. Seven new mutations were identified in 15 of 16 mutated alleles, including six point mutations: T416I (4 alleles), G390R (1 allele), and S305L, A293T, L283P, and G1O1R (2 alleles each). In addition, a 1-bp deletion at position 1173 was identified in two alleles. These findings do not provide a molecular basis for the clinical variability in GA-I families. The occurrence of multiple novel mutations in a small geographic area may be explained by their recent onset in isolated communities with a high consanguinity rate.
对8个患有I型戊二酸血症（GA-I）的家族（16名患者）进行了突变分析，这些家族是1987年至1994年期间在以色列确诊的所有家族。其中6个家族为穆斯林血统，2个为非阿什肯纳兹犹太人。对每个家族的1名患者的戊二酰辅酶A脱氢酶基因cDNA的整个编码区进行了测序。在16个突变等位基因中的15个中鉴定出7个新突变，包括6个点突变：T416I（4个等位基因）、G390R（1个等位基因）、S305L、A293T、L283P和G1O1R（各2个等位基因）。此外，在两个等位基因中鉴定出1173位的1个碱基缺失。这些发现并未为GA-I家族的临床变异性提供分子基础。在一个小地理区域内出现多个新突变可能是由于它们在近亲结婚率高的孤立社区中近期才开始出现。
