Hara Y, Ioannou P, Drousiotou A, Stylianidou G, Anastasiadou V, Suzuki K
Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599.
Hum Genet. 1994 Aug;94(2):136-40. doi: 10.1007/BF00202858.
Sandhoff disease occurs in the Christian Maronite community in Cyprus, a community that established over a thousand years ago. Nowadays, this community comprises less than 1% of the whole population, and has been culturally and socially isolated. Cultured fibroblasts from a patient from this inbred group showed a beta-hexosaminidase beta subunit mRNA of apparently the normal size but of reduced quantity. A mutational analysis of cDNA obtained by polymerase chain reaction amplification of mRNA showed a deletion of A at nt 76 (counted from A of the initiation codon, ATG). The deletion results in a frame shift and a premature termination within 20 amino acids from the N-terminus of the normal mature enzyme protein. The patient was homozygous for the deletion. The 5'-end of the gene showed many discrepancies from the previously published sequence. We consider that these differences are probably polymorphisms of little functional significance, because the patient's fibroblasts generate decreased but stable mRNA and because some of these base changes were also found in the genes from control fibroblasts. An extensive evaluation of the prevalence of this mutant allele in this community is being initiated.
桑德霍夫病发生在塞浦路斯的基督教马龙派社区，该社区建立于一千多年前。如今，这个社区占总人口的比例不到1%，在文化和社会层面上处于隔离状态。从这个近亲群体的一名患者身上获取的培养成纤维细胞显示，β-己糖胺酶β亚基的信使核糖核酸（mRNA）大小看似正常，但数量减少。通过对信使核糖核酸进行聚合酶链反应扩增得到的互补脱氧核糖核酸（cDNA）进行突变分析，结果显示在第76个核苷酸处（从起始密码子ATG的A开始计数）缺失了一个A。这种缺失导致移码，并在正常成熟酶蛋白N端的20个氨基酸内提前终止。该患者的这种缺失是纯合的。该基因的5'端与之前发表的序列存在许多差异。我们认为这些差异可能是功能意义不大的多态性，因为患者的成纤维细胞产生的信使核糖核酸数量减少但稳定，而且在对照成纤维细胞的基因中也发现了其中一些碱基变化。目前正在对这个社区中这种突变等位基因的流行情况进行广泛评估。
