title: Evaluation of clinical diagnosis criteria of familial ligand defective apoB 100 and lipoprotein phenotype comparison between LDL receptor gene mutations affecting ligand-binding domain and the R3500Q mutation of the apoB gene in patients from a South European population.
abstract: Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are characterized by increased plasma low-density lipoprotein cholesterol (LDLc) levels and risk of coronary heart disease (CHD). FDB is clinically indistinguishable from FH. The aims of this study were to evaluate clinical diagnosis criteria for FDB and to compare the lipoprotein phenotype between carriers of LDL receptor (LDLR) gene mutations that affect the ligand-binding domain and subjects with the R3500Q mutation in apoB gene. We studied 213 subjects (113 probands) with FH and 19 heterozygous FDB subjects. Genetic diagnosis was determined by following a protocol based on Southern blot and polymerase chain reaction-single strand conformation polymorphism (SSCP) analysis. Thirty FH carriers of LDLR gene missense mutations that affect ligand-binding domain were matched by age, gender, and body mass index to the 19 FDB subjects (R3500Q mutation). Lipoprotein phenotype comparison was conducted between the 2 groups. FH patients showed plasma total and LDL cholesterol levels significantly higher than those in FDB patients. Three FDB showed plasma total and LDLc values in the normal range. Using the 1999 clinical Med-Ped criteria for diagnosis of genetic hypercholesterolemia, no FDB subjects had a confirmed diagnosis; it was probable in 36% of the subjects, it was possible in 32% of the subjects, and it could be excluded in the remaining 32% of the subjects. We conclude that the FDB lipoprotein phenotype was significantly less severe than that observed in FH carriers of LDLR gene missense ligand-binding domain mutations. Clinical Med-Ped diagnosis criteria tend to under-diagnose FDB.
authors.affiliation: Service of Endocrinology and Nutrition, Hospital Clinico Universitario, Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Ejarque
authors.forename: Jose T
authors.initials: JT
authors.lastname: Real
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinez-Hervas
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Chaves
authors.forename: Sebastian
authors.initials: S
authors.lastname: Blesa
authors.forename: Ana B
authors.initials: AB
authors.lastname: Garcia-Garcia
authors.forename: Enrique
authors.initials: E
authors.lastname: Millan
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood / Q000235:genetics*; D001665:Binding Sites; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005060:Europe; D005260:Female; D018703:Founder Effect; D006580:Genetic Carrier Screening; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D011973:Receptors, LDL