Mutation analysis of a Sandhoff disease patient in the Maronite community in Cyprus.
Mutation analysis of a Sandhoff disease patient in the Maronite community in Cyprus.
复制标题
塞浦路斯马龙派社区一名桑霍夫病患者的突变分析。
DOI：
10.1007/bf00202858
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发表时间：
1994
期刊：
影响因子：
5.3
通讯作者：
Suzuki,K
中科院分区：
文献类型：
--
作者：
Hara,Y;Ioannou,P;Drousiotou,A;Stylianidou,G;Anastasiadou,V;Suzuki,K
桑德霍夫病发生在塞浦路斯的基督教马龙派社区，这个社区成立于一千多年前。如今，这个社区只占总人口的不到1%，在文化和社会上都是孤立的。培养的近交系患者成纤维细胞显示β-氨基己糖苷酶β亚单位明显大小正常，但数量减少。通过聚合酶链式反应扩增获得的mRNA的突变分析显示，在第76个核苷酸(从起始密码子ATG的A开始计算)处有A的缺失。缺失导致正常成熟酶蛋白N端20个氨基酸内的移码和提前终止。患者是缺失的纯合子。该基因的5‘端与之前发表的序列有许多差异。我们认为这些差异可能是功能意义不大的多态，因为患者的成纤维细胞产生的mRNA减少但稳定，而且其中一些碱基变化也在对照成纤维细胞的基因中发现。对该突变等位基因在该社区中的流行率的广泛评估正在启动。
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 β-hexosaminidase β 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.