title: Genetic heterogeneity of autosomal dominant hypercholesterolemia in Mexico.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apoB) genes, respectively. A third locus on chromosome 1p34.1-p32 was recently linked to FH and the responsible gene has been identified [protein convertase subtilisin/kexin type 9 (PCSK9)].
  
  
  METHODS
  We assessed the contribution of the LDLR, apoB, and PCSK9 genes as cause of FH in Mexico. Forty six unrelated probands, as well as 68 affected and 60 healthy relatives, were included.
  
  
  RESULTS
  All index cases were diagnosed as having heterozygous autosomal dominant FH. Seventeen of the 46 index cases had LDLR gene mutations, four of which were novel (Fs92ter108, C268R, Q718X, and Fs736ter743); and only one patient had an apoB mutation (R3500Q). We sequenced the PCSK9 gene in the remainder of the 28 probands with no identified LDLR or APOB gene defects; however, no PCSK9 mutations were found, including one large kindred with positive linkage to the 1p34.1-32 locus (multipoint LOD score of 3.3) and two small pedigrees. Linkage was excluded from these three loci in at least four kindreds suggesting that other yet uncharacterized genes are involved.
  
  
  CONCLUSIONS
  Our results underline substantial genetic heterogeneity for FH in the Mexican population.
authors.affiliation: Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., Mexico.
authors.forename: Ludivina
authors.initials: L
authors.lastname: Robles-Osorio
authors.forename: Alejandra
authors.initials: A
authors.lastname: Huerta-Zepeda
authors.forename: Ma Luisa
authors.initials: ML
authors.lastname: Ordóñez
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: Andrea
authors.initials: A
authors.lastname: Díaz-Villaseñor
authors.forename: Ruth
authors.initials: R
authors.lastname: Gutiérrez-Aguilar
authors.forename: Laura
authors.initials: L
authors.lastname: Riba
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vázquez
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodríguez-Torres
authors.forename: Rita A
authors.initials: RA
authors.lastname: Gómez-Díaz
authors.forename: Saul
authors.initials: S
authors.lastname: Salinas
authors.forename: Laura
authors.initials: L
authors.lastname: Ongay-Larios
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Codiz-Huerta
authors.forename: Minerva
authors.initials: M
authors.lastname: Mora-Cabrera
authors.forename: Roopa
authors.initials: R
authors.lastname: Mehta
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Gómez Pérez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rull
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rabès
authors.forename: Ma Teresa
authors.initials: MT
authors.lastname: Tusié-Luna
authors.forename: Socorro
authors.initials: S
authors.lastname: Durán-Vargas
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008800:Mexico; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D040641:Quantitative Trait Loci; D011973:Receptors, LDL / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases