Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene
Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene
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DOI：
10.1097/01.gim.0000237720.78475.fb
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发表时间：
2006-10-01
影响因子：
8.8
通讯作者：
Muralidharan, Kasinathan
中科院分区：
文献类型：
--
作者：
Coffee, Bradford;Hjelm, Lawrence N.;Muralidharan, Kasinathan
目的：我们以前报道了一个缺失的半乳糖-1-磷酸尿苷转移酶（GALT）基因。这种缺失可以导致位于相对等位基因上的变体的表观纯合性，潜在地导致个体中的生化表型和表观基因型之间的差异。本研究的目的是确定缺失断裂点，允许开发用于突变的快速可靠的分子测试。方法：采用聚合酶链反应步移法（Polymerase Chain Reaction walking strategy）定位5'和3'断裂点。扩增连接片段并测序以精确表征缺失断点。结果：该缺失具有二分结构，涉及GALT基因的两个大片段，同时保留该基因的一个短的内部片段。分子表征允许开发基于缺失特异性聚合酶链反应的测定。在25例具有生化携带者半乳糖血症表型，但对8种常见GALT基因变异体检测呈阴性的个体中，3例携带这种缺失。结论-这种缺失发生在一个明显的频率，并应考虑当有一个基因型和生化表型之间的差异。许多携带该等位基因的个体是德系犹太人的祖先，这表明该缺失可能是该人群中半乳糖血症的常见原因。
Purpose: We previously reported a deletion of the Galactose-l-Phosphate Uridyl Transferase (GALT) gene. This deletion can cause apparent homozygosity for variants located on the opposite allele, potentially resulting in a discrepancy between the biochemical phenotype and the apparent genotype in an individual. The purpose of this study was to determine the deletion breakpoints, allowing the development of a rapid and reliable molecular test for the mutation. Methods: A Polymerase Chain Reaction walking strategy was used to map the 5' and 3' breakpoints. The junction fragment was amplified and sequenced to precisely characterize the deletion breakpoints. Results: The deletion has a bipartite structure involving two large segments of the GALT gene, while retaining a short internal segment of the gene. Molecular characterization allowed the development of a deletion specific Polymerase Chain Reaction-based assay. In 25 individuals who had a biochemical carrier galactosemia phenotype, but tested negative for 8 common GALTgene variants, 3 carried this deletion. Conclusion- This deletion occurs at an appreciable frequency and should be considered when there is a discrepancy between the genotype and biochemical phenotype. Many of the individuals carrying the allele were of Ashkenazi Jewish ancestry suggesting that the deletion may be a common cause of galactosemia in that population.