title: Screening for point mutations in the LDL receptor gene in Bulgarian patients with severe hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is a common, autosomal dominant disorder of lipid metabolism, caused by defects in the receptor-mediated uptake of LDL (low-density lipoproteins) due to mutations in the LDL receptor gene ( LDLR). Mutations underlying FH in Bulgaria are largely unknown. The aim of the present study was to provide information about the spectrum of point mutations in LDLR in a sample of 45 Bulgarian patients with severe hypercholesterolemia. Exons 3, 4, 6, 8, 9, and 14, previously shown to be mutational hot spots in LDLR, were screened using PCR-single-strand conformation polymorphism (SSCP). Samples with abnormal SSCP patterns were sequenced. Three different, hitherto undescribed point mutations (367T>A, 377T>A, 917C>A) and two previously described mutations (858C>A and 1301C>T) in eight unrelated patients were identified; four of the detected point mutations being missense mutations and one, a nonsense mutation. One of the newly described point mutations (917C>A) is a base substitution at a nucleotide position, at which two other different base substitutions have already been reported. Thus, all three possible base substitutions at this nucleotide position have been detected, making it a hot spot for point mutations causing FH. This is the first such mutational hot spot described in exon 6 of LDLR.
authors.affiliation: Department of Chemistry and Biochemistry, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria.
authors.forename: Vassil A
authors.initials: VA
authors.lastname: Mihaylov
authors.affiliation: Department of Chemistry and Biochemistry, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria.
authors.forename: Anelia D
authors.initials: AD
authors.lastname: Horvath
authors.affiliation: University Hospital for Obstetrics and Gynaecology, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Savov
authors.affiliation: Department of Propaedeutics of Internal Diseases, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria.
authors.forename: Elina F
authors.initials: EF
authors.lastname: Kurshelova
authors.affiliation: National Centre of Cardiovascular Diseases, Sofia, Bulgaria.
authors.forename: Ivanka D
authors.initials: ID
authors.lastname: Paskaleva
authors.affiliation: Department of Propaedeutics of Internal Diseases, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria.
authors.forename: Assen R
authors.initials: AR
authors.lastname: Goudev
authors.affiliation: Department of Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Ivaylo R
authors.initials: IR
authors.lastname: Stoilov
authors.affiliation: Department of Chemistry and Biochemistry, Medical University of Sofia, 2 Zdrave Str., Sofia, 1431, Bulgaria. ganev@medfac.acad.bg.
authors.forename: Varban S
authors.initials: VS
authors.lastname: Ganev
mesh_terms: D002031:Bulgaria / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL; D004247:DNA