title: Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis.
abstract: Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1.
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: Susan V
authors.initials: SV
authors.lastname: Smalley
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile . ; School of Medicine, Universidad Diego Portales, Santiago, Chile .
authors.forename: Yudith
authors.initials: Y
authors.lastname: Preiss
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile . ; Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile .
authors.forename: José
authors.initials: J
authors.lastname: Suazo
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: Javier Andrés
authors.initials: JA
authors.lastname: Vega
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: Isidora
authors.initials: I
authors.lastname: Angellotti
authors.affiliation: Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lagos
authors.affiliation: Faculty of Medicine, Universidad de Valparaíso, Valparaíso, Chile . ; Department of Neurology, Hospital Carlos Van Buren, Valparaíso, Chile .
authors.forename: Enzo
authors.initials: E
authors.lastname: Rivera
authors.affiliation: Faculty of Medicine, Universidad de Chile, Santiago, Chile . ; Clínica Las Condes, Santiago, Chile .
authors.forename: Karin
authors.initials: K
authors.lastname: Kleinsteuber
authors.affiliation: Department of Food Sciences and Physiology, Universidad de Navarra, Pamplona, Spain .
authors.forename: Javier
authors.initials: J
authors.lastname: Campion
authors.affiliation: Department of Food Sciences and Physiology, Universidad de Navarra, Pamplona, Spain .
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: Alberto
authors.initials: A
authors.lastname: Maiz
authors.affiliation: Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile .
authors.forename: José Luis
authors.initials: JL
authors.lastname: Santos
keywords: Cerebrotendinous Xanthomatosis; exon skipping; mutation; splicing