title: Recurrent and novel LDL receptor gene mutations causing heterozygous familial hypercholesterolemia in La Habana.
abstract: The molecular basis of familial hypercholesterolemia (FH) in three families of Spanish descent from La Habana was investigated by the candidate gene approach. The Arg3500Gln mutation of apolipoprotein B-100 was not found. Identification of low density lipoprotein receptor (LDLR) gene haplotypes segregating with FH guided the characterisation of three point mutations by automated sequencing. One, a Val408-->Met missense mutation, a founder mutation in Afrikaner FH patients, was recurrent, being associated with a distinct DNA haplotype. The other two, Glu256-->Lys and Val776-->Met missense mutations, were novel and modified highly conserved residues. These mutations were absent in normolipidemic subjects and were associated in heterozygous carriers with twice the cholesterol levels observed in non-carriers. Noticeably, cardiovascular complications were rarely observed in older heterozygotes, even in those with the Afrikaner FH-2 mutation. These findings confirm the molecular heterogeneity of LDLR gene mutations causing FH and the variability of their expression across different populations.
authors.affiliation: Hospital Hermanos Ameijeiras, La Habana, Cuba.
authors.forename: E
authors.initials: E
authors.lastname: Pereira
authors.forename: R
authors.initials: R
authors.lastname: Ferreira
authors.forename: B
authors.initials: B
authors.lastname: Hermelin
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Bernard
authors.forename: V
authors.initials: V
authors.lastname: Bertrand
authors.forename: H
authors.initials: H
authors.lastname: Nassiff
authors.forename: D
authors.initials: D
authors.lastname: Mendez del Castillo
authors.forename: G
authors.initials: G
authors.lastname: Bereziat
authors.forename: P
authors.initials: P
authors.lastname: Benlian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D003462:Cuba; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011973:Receptors, LDL / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides