McInnes B, Brown C A, Mahuran D J
Research Institute, Hospital for Sick Children, Toronto, Canada.
Biochim Biophys Acta. 1992 Apr 14;1138(4):315-7. doi: 10.1016/0925-4439(92)90009-c.
Lysosomal beta-hexosaminidase (EC 3.2.1.52) occurs as two major isozymes hexosaminidase A (alpha beta) and B (beta beta). The alpha subunit is encoded by the HEXA gene and the beta subunit by HEXB gene. Defects in the alpha or beta subunits lead to Tay-Sachs or Sandhoff disease, respectively. While many HEXA gene mutations have been reported only three HEXB gene mutations are known. We report the characterization of two rare HEXB mutations present in genomic DNA from a single fibroblast cell line, GM203, taken from a patient with the infantile form of Sandhoff disease. The first is a single base pair deletion in exon 7 changing the codon for Gly-258, GGA, to GA and the second, a two base pair deletion in exon 11 changes the codons for Arg-435/Val-436, AGA/GTC, to AGTC. Each mutation produces a frame shift in the affected allele that results in a premature stop codon 17 or 20 codons downstream, respectively. These mutations also result in the inability to detect beta-mRNA by Northern blot analysis of total mRNA. These data are consistent with the idea that the severe infantile form of Tay-Sachs or Sandhoff disease is associated with a total lack of residual hexosaminidase A activity.
溶酶体β-己糖胺酶（EC 3.2.1.52）以两种主要同工酶己糖胺酶A（αβ）和B（ββ）的形式存在。α亚基由HEXA基因编码，β亚基由HEXB基因编码。α或β亚基的缺陷分别导致泰-萨克斯病或桑德霍夫病。虽然已经报道了许多HEXA基因突变，但已知的HEXB基因突变只有三种。我们报告了从一名患有婴儿型桑德霍夫病的患者的单个成纤维细胞系GM203的基因组DNA中存在的两种罕见HEXB突变的特征。第一种是外显子7中的单个碱基对缺失，将甘氨酸-258的密码子GGA变为GA，第二种是外显子11中的两个碱基对缺失，将精氨酸-435/缬氨酸-436的密码子AGA/GTC变为AGTC。每个突变在受影响的等位基因中产生移码，分别导致下游17或20个密码子处出现提前终止密码子。这些突变还导致通过对总mRNA进行Northern印迹分析无法检测到β- mRNA。这些数据与以下观点一致，即严重的婴儿型泰-萨克斯病或桑德霍夫病与完全缺乏残留的己糖胺酶A活性有关。
