Mules E H, Dowling C E, Petersen M B, Kazazian H H, Thomas G H
Genetics Laboratory, Kennedy Institute, Baltimore, MD 21205.
Am J Hum Genet. 1991 Jun;48(6):1181-5.
Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration.
对三名具有典型婴儿型泰-萨克斯病生化和临床特征的无血缘关系的美国黑人婴儿的基因组DNA样本进行PCR扩增后测序。在第一个黑人家庭中，β-己糖胺酶α亚基基因第5外显子之前的AG受体剪接位点观察到一个G→T颠换。这种颠换将受体剪接位点从共有序列AG变为AT，从而干扰了内含子4/外显子5连接处的剪接。先证者为该突变的纯合子；他的母亲和一个兄弟为杂合子。在第二名显然无血缘关系的黑人GM2神经节苷脂沉积症患者中发现了相同的突变。第二名患者是复合杂合子，因为只有一个等位基因携带该突变。第二个家庭的母亲和一个兄弟是该突变的携带者，而父亲和一个非携带者姐妹在该基因区域是正常的。第三名先证者没有这种突变；第四名黑人先证者的母亲也没有。其他八个独立确定的非黑人、非犹太GM2神经节苷脂沉积症家庭没有这种突变。在两名无血缘关系的黑人GM2神经节苷脂沉积症患者中观察到相同的新突变，这表明美国黑人人群中至少有一个GM2神经节苷脂沉积症突变在该人群中分离，这可能是该人群特有的，而非迁移的结果。
