title: Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.
abstract: The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 -1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype-phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico.
authors: Divisiòn de Genètica, Centro de Investigaciòn Biomèdica de Occidente, IMSS, Guadalajara, Jalisco, Mexico. gvacap@yahoo.com
authors: Gerardo
authors: G
authors: Vaca
authors: Alejandra
authors: A
authors: Vàzquez
authors: Marìa Teresa
authors: MT
authors: Magaña
authors: Marìa Lourdes
authors: ML
authors: Ramìrez
authors: Ingrid P
authors: IP
authors: Dàvalos
authors: Esperanza
authors: E
authors: Martìnez
authors: Bertha
authors: B
authors: Marìn
authors: Gabriela
authors: G
authors: Carrillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001055:Apolipoproteins B / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D011973:Receptors, LDL; D002784:Cholesterol