A Novel Pathogenic Nonsense Triple-Nucleotide Mutation in the Low-Density Lipoprotein Receptor Gene and Its Clinical Correlation with Familial Hypercholesterolemia

作者：Ajmal Muhammad; Ahmed Waqas; Akhtar Naveed; Sadeque Ahmed; Khalid Ayesha; Ali Syeda Hafiza Benish; Ahmed Nuzhat; Azam Maleeha; Qamar Raheel^*

来源：Genetic Testing and Molecular Biomarkers, 2011, 15(9): 601-606.

DOI：10.1089/gtmb.2010.0184

Aim: The aim of this study was to determine the genetic basis of familial hypercholesterolemia in a Pakistani family with a history of myocardial infarction and premature coronary artery disease. Results: Direct sequencing of the low-density lipoprotein receptor gene resulted in the identification of a novel missense mutation c.264G>C (p.R88S) in exon 3 and a novel nonsense triple-nucleotide polymorphism (TNP) c.887-889GCA>AGC (p.C296X) in exon 6, the latter being probably the disease-causing mutation in this family. Both of these mutations were not present in the probands of 14 familial hypercholesterolemia families, 100 myocardial infarction patients, as well as 150 normolipidemic ethnically matched control individuals. Conclusions: The identification of the novel nonsense TNP is the first report of a nonsense pathogenic TNP in low-density lipoprotein receptor or any other gene and only the fourth report of a pathogenic TNP of any type, which emphasizes the importance of screening for TNPs in patients and in familial studies that might otherwise be missed if only analyzed on single-nucleotide polymorphism arrays.

• 出版日期2011-9