Ohno K, Suzuki K
Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599.
Biochem Biophys Res Commun. 1988 May 31;153(1):463-9. doi: 10.1016/s0006-291x(88)81247-6.
Abnormal beta-hexosaminidase alpha chain mRNAs from an Ashkenazi Jewish patient with the classical infantile Tay-Sachs disease contained intact or truncated intron 12 sequences. Sequence analysis showed a single nucleotide transversion at the 5' donor site of intron 12 from the normal G to C. This provides the first evidence that this junctional mutation, also found independently in two other laboratories by analysis of genomic clones, results in functional abnormality. Analysis with normal and mutant oligonucleotides as probes indicated that our patient was a compound heterozygote with only one allele having the transversion. The patient studied in the other two laboratories was also a compound heterozygote. Another Ashkenazi Jewish patient was normal in this region in both alleles. Thus, the splicing defect is the underlying genetic cause in some but not all Ashkenazi Jewish patients with Tay-Sachs disease.
一名患有典型婴儿型泰-萨克斯病的阿什肯纳兹犹太患者的异常β-己糖胺酶α链mRNA包含完整或截短的内含子12序列。序列分析显示，内含子12的5'供体位点处有一个单核苷酸颠换，从正常的G变为C。这首次证明了这种连接突变（另外两个实验室通过分析基因组克隆也独立发现了该突变）会导致功能异常。用正常和突变的寡核苷酸作为探针进行分析表明，我们的患者是复合杂合子，只有一个等位基因发生了颠换。在另外两个实验室研究的患者也是复合杂合子。另一名阿什肯纳兹犹太患者在该区域的两个等位基因均正常。因此，剪接缺陷是部分而非所有阿什肯纳兹犹太泰-萨克斯病患者的潜在遗传病因。
