title: A novel pathogenic nonsense triple-nucleotide mutation in the low-density lipoprotein receptor gene and its clinical correlation with familial hypercholesterolemia.
abstract: OBJECTIVE
  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.
authors: COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors: Muhammad
authors: M
authors: Ajmal
authors: Waqas
authors: W
authors: Ahmed
authors: Naveed
authors: N
authors: Akhtar
authors: Ahmed
authors: A
authors: Sadeque
authors: Ayesha
authors: A
authors: Khalid
authors: Syeda Hafiza
authors: SH
authors: Benish Ali
authors: Nuzhat
authors: N
authors: Ahmed
authors: Maleeha
authors: M
authors: Azam
authors: Raheel
authors: R
authors: Qamar
mesh_terms: D000328:Adult; D018389:Codon, Nonsense / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009711:Nucleotides / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000502:physiology; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D009711:Nucleotides; D011973:Receptors, LDL