title: Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani arab family with familial hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman Familial Hypercholesterolemia Study Group, Oman Society of Lipid and Atherosclerosis (OSLA), Sultan Qaboos University, Muscat, Oman.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Rasadi
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman Familial Hypercholesterolemia Study Group, Oman Society of Lipid and Atherosclerosis (OSLA), Sultan Qaboos University, Muscat, Oman.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Waili
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Ward Al-Muna
authors.initials: WA
authors.lastname: Al-Zidi
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman Familial Hypercholesterolemia Study Group, Oman Society of Lipid and Atherosclerosis (OSLA), Sultan Qaboos University, Muscat, Oman.
authors.forename: Abdul Rahim
authors.initials: AR
authors.lastname: Al-Abri
authors.affiliation: Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Ali T
authors.initials: AT
authors.lastname: Al-Hinai
authors.affiliation: Department of Surgery, Cardiothoracic Surgery Division, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Hilal Ali
authors.initials: HA
authors.lastname: Al-Sabti
authors.affiliation: Department of Clinical Biochemistry, Medical Laboratory Science program, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Sheikha
authors.initials: S
authors.lastname: Al-Tobi
authors.affiliation: Department of Pharmacology & Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Zakwani
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Zadjali
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Khamis
authors.initials: K
authors.lastname: Al-Hashmi
authors.affiliation: Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman Familial Hypercholesterolemia Study Group, Oman Society of Lipid and Atherosclerosis (OSLA), Sultan Qaboos University, Muscat, Oman yaj.banerjee@gmail.com.
authors.forename: Yajnavalka
authors.initials: Y
authors.lastname: Banerjee
mesh_terms: D000293:Adolescent; D000328:Adult; D018912:Arabs / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009850:Oman; D010375:Pedigree; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL
keywords: LDL receptor; Oman; Omani Arab; familial hypercholesterolemia; in silico