Navon R, Proia R L
Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892.
Science. 1989 Mar 17;243(4897):1471-4. doi: 10.1126/science.2522679.
The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive disorder that results from mutations in the alpha chain of beta-hexosaminidase A. This disorder, like infantile Tay-Sachs disease, is more frequent in the Ashkenazi Jewish population. A point mutation in the alpha-chain gene was identified that results in the substitution of Gly with Ser in eight Ashkenazi adult GM2 gangliosidosis patients from five different families. This amino acid substitution was shown to depress drastically the catalytic activity of the alpha chain after expression in COS-1 cells. All of these patients proved to be compound heterozygotes of the allele with the Gly to Ser change and one of the two Ashkenazi infantile Tay-Sachs alleles. These findings will aid in the diagnosis and understanding of beta-hexosaminidase A deficiency disorders.
成人型泰-萨克斯病，即成人GM2神经节苷脂贮积症，是一种常染色体隐性疾病，由β-己糖胺酶A的α链突变引起。这种疾病与婴儿型泰-萨克斯病一样，在阿什肯纳兹犹太人群中更为常见。在来自五个不同家庭的八名阿什肯纳兹成人GM2神经节苷脂贮积症患者中，发现α链基因存在一个点突变，导致甘氨酸被丝氨酸取代。在COS-1细胞中表达后，这种氨基酸取代被证明会大幅降低α链的催化活性。所有这些患者均被证明是甘氨酸到丝氨酸变化的等位基因与两个阿什肯纳兹婴儿型泰-萨克斯等位基因之一的复合杂合子。这些发现将有助于β-己糖胺酶A缺乏症的诊断和理解。
