title: Screening of APOB gene mutations in subjects with clinical diagnosis of familial hypercholesterolemia.
abstract: Monogenic hypercholesterolemia is a group of lipid disorders, most of which have autosomal dominant transmission. Familial defective apoB (FDB) resulting from mutations in the APOB gene is a well-recognized cause of autosomal dominant monogenic hypercholesterolemia (ADMH). However, the frequency of FDB among patients with ADMH is not well established. The aim of our research was to screen for mutations responsible for FDB in subjects with a clinical diagnosis of familial hypercholesterolemia. We studied 408 patients from the Spanish Register of Familial Hypercholesterolemia, proportionally distributed among all Spanish regions. Abnormal SSCP patterns of the APOB gene were checked by DNA sequencing and restriction analysis. Three out of the 408 patients were carriers of the R3500Q mutation, and 2 subjects were carriers of the silent T3552T mutation; in both of these patients functional mutations in the LDL receptor gene were found. We conclude that FDB is not a common cause of ADMH in Spain; the R3500Q mutation is the only mutation in APOB causing FDB, and the LDL receptor binding domain of APOB is highly conserved in the studied sample.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Plaza San Francisco s/n, 50009 Zaragoza, Spain.
authors.forename: Erardo
authors.initials: E
authors.lastname: Meriño-Ibarra
authors.forename: Sergio
authors.initials: S
authors.lastname: Castillo
authors.forename: Pilar
authors.initials: P
authors.lastname: Mozas
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.forename: Esperanza
authors.initials: E
authors.lastname: Martorell
authors.forename: José Luis
authors.initials: JL
authors.lastname: Díaz
authors.forename: Manuel
authors.initials: M
authors.lastname: Suárez-Tembra
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocoví
mesh_terms: D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D025063:Chromosome Disorders / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012042:Registries; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires
chemical_list: D001055:Apolipoproteins B