Drucker L, Hemli J A, Navon R
Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
Hum Mutat. 1997;10(6):451-7. doi: 10.1002/(SICI)1098-1004(1997)10:6<451::AID-HUMU6>3.0.CO;2-G.
Two affected HEXA alleles were found in an Israeli Druze Tay-Sachs child born to first-cousin parents. His paternal allele contained two adjacent changes in exon 5: delta496C, which resulted in a frameshift and premature termination codon 96 nucleotides downstream, and 498C-->G, a silent mutation. The maternal allele had a 835T-->C transition in exon 8 (S279P). Phosphoimaging quantitation of the parents' RNAs showed that the steady-state levels of mRNAs of the mutant exons 5 and 8 were 5% and 50%, respectively, of normal levels. The exon 5 mutated allele with the premature translation termination resulted in severe deficiency of Hex A. Transient expression of the exon 8 mutated alpha-chain cDNA in COS-1 cells resulted in deficiency of enzymatic activity. The child exhibited a late-infantile-type disease.
在一对表亲父母所生的一名以色列德鲁兹族患泰-萨克斯病的儿童中发现了两个受影响的HEXA等位基因。其父亲的等位基因在第5外显子中有两个相邻变化：delta496C，导致移码并在下游96个核苷酸处出现过早终止密码子，以及498C→G，一个沉默突变。母亲的等位基因在第8外显子中有一个835T→C转换（S279P）。对父母RNA的磷酸成像定量显示，突变的第5和第8外显子mRNA的稳态水平分别为正常水平的5%和50%。具有过早翻译终止的第5外显子突变等位基因导致Hex A严重缺乏。第8外显子突变的α链cDNA在COS-1细胞中的瞬时表达导致酶活性缺乏。该儿童表现出晚发性婴儿型疾病。
