McDowell G A, Mules E H, Fabacher P, Shapira E, Blitzer M G
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
Am J Hum Genet. 1992 Nov;51(5):1071-7.
A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the beta-hexosaminidase A (Hex A) alpha-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes. The mutation in the remaining allele was a single-base transition in the donor splice site of the alpha-subunit intron 9. To determine the origins of these two mutations in the Cajun population, the TSD carrier status was enzymatically determined for 90 members of four of the six families, and extensive pedigrees were constructed for all carriers. A single ancestral couple from France was found to be common to most of the carriers of the exon 11 insertion. Pedigree data suggest that this mutation has been in the Cajun population since its founding over 2 centuries ago and that it may be widely distributed within the population. In contrast, the intron 9 mutation apparently was introduced within the last century and probably is limited to a few Louisiana families.
开展了一项研究，旨在鉴定路易斯安那州西南部法裔加拿大人中导致泰-萨克斯病（TSD）的突变，并确定这些突变的起源。在六个家族中检测的12个婴儿型TSD等位基因中，有11个具有β-己糖胺酶A（Hex A）α亚基第11外显子插入突变，该突变约存在于70%的德系犹太TSD杂合子中。其余等位基因中的突变是α亚基第9内含子供体剪接位点的单碱基转换。为了确定法裔加拿大人群体中这两种突变的起源，对六个家族中四个家族的90名成员进行了酶学检测以确定其TSD携带者状态，并为所有携带者构建了详细的家系图谱。发现大多数第11外显子插入突变的携带者都有一对来自法国的共同祖先夫妇。家系数据表明，这种突变自两个多世纪前法裔加拿大人群体形成以来就已存在，并且可能在该群体中广泛分布。相比之下，第9内含子突变显然是在上个世纪引入的，可能仅限于路易斯安那州的少数几个家族。
