title: Two novel mutations in the ABCG5 gene, c.144 -1G>A and c.1523 delC, in a Mexican family with sitosterolemia.
abstract: Sitosterolemia is a disease characterized by an intestinal hyperabsorption of plant sterols and cholesterol. Affected individuals have mutations in both alleles of either ABCG5 or ABCG8 genes, leading to a total loss of one of the proteins and subsequent functional deficiency. We here report a Mexican family with clinical and biochemical features of sitosterolemia carrying 2 new mutations of the ABCG5 gene. Concentrations of sitosterol, campesterol, and cholesterol were found to be higher for the index case (a 10-year-old girl) than for her also affected sibling (64.1 vs 19 mg/dL, 32 vs 12.1 mg/dL, and cholesterol 295 vs 235 mg/dL, respectively). Both individuals showed 2 new ABCG5 gene mutations identified by sequencing, which is concordant with their biochemical diagnosis of sitosterolemia. The first mutation was a c.144 -1G>A transition that disrupts the intron 1 splicing acceptor site. The second mutation is the deletion c.1523 delC, which occurred in exon 11, causing an amino acid change at codon 510 (p.His510Thr) and a stop codon at codon 511 (p.Leu511X). The father is heterozygote for the mutation c.144 -1G>A, whereas the mother is heterozygote for the mutation c.1523 delC. In conclusion, we here report the first case of a Mexican family with sitosterolemia carrying two new ABCG5 gene mutations.
authors.affiliation: División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México; Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Colima Fausto
authors.affiliation: División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: González García
authors.affiliation: Hospital Civil "Dr. Antonio González Guevara", Departamento de Genética, Tepic, Nayarit, Mexico.
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Wong Ley Madero
authors.affiliation: División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México. Electronic address: maganamt@yahoo.com.mx.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Magaña Torres
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D001483:Base Sequence; D002648:Child; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007410:Intestinal Diseases / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010840:Phytosterols / Q000009:adverse effects* / Q000235:genetics; D055815:Young Adult
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D010840:Phytosterols
keywords: ABCG5 gene; First Mexican family with sitosterolemia; Phenotypic heterogeneity; Sitosterolemia; c.144 -1G>A mutation; c.1523 delCmutation