Narkis G, Adam A, Jaber L, Pennybacker M, Proia R L, Navon R
Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
Hum Mutat. 1997;10(6):424-9. doi: 10.1002/(SICI)1098-1004(1997)10:6<424::AID-HUMU2>3.0.CO;2-D.
Genotyping individuals for Tay-Sachs disease (TSD) is mainly based on the heat lability of beta-hexosaminidase (Hex) A (alphabeta) and the heat stability of Hex B (betabeta). Mutations in the HEXB gene encoding the beta-subunits of Hex that result in heat-labile Hex B thus may lead to erroneous enzymatic genotyping regarding TSD. Utilizing single strand conformation polymorphism (SSCP) analysis for all 14 exons of HEXB followed by direct sequencing of aberrant fragments, we screened individuals whose Hex B was heat labile. A novel heat labile mutation, previously concluded to exist in the HEXB gene, was identified among Jews and Arabs as 1627 G-->A. One individual with heat labile Hex B (HLB) was negative for this novel mutation and for the known 1514 G-->A HLB mutation, proving that there exists at least one other unidentified HLB mutation. Based on these results, it is advisable to perform DNA tests for 1627 G-->A mutation in suspected HLB individuals.
对个体进行泰-萨克斯病（TSD）基因分型主要基于β-己糖胺酶（Hex）A（αβ）的热不稳定性和Hex B（ββ）的热稳定性。编码Hexβ亚基的HEXB基因发生突变，导致产生热不稳定的Hex B，因此可能导致关于TSD的酶促基因分型出现错误。我们利用单链构象多态性（SSCP）分析HEXB基因的所有14个外显子，随后对异常片段进行直接测序，对Hex B热不稳定的个体进行了筛查。在犹太人和阿拉伯人中，一个先前推断存在于HEXB基因中的新型热不稳定突变被鉴定为1627 G→A。一名Hex B热不稳定（HLB）个体对该新型突变和已知的1514 G→A HLB突变均呈阴性，这证明至少还存在另一种未被识别的HLB突变。基于这些结果，建议对疑似HLB个体进行1627 G→A突变的DNA检测。
