title: Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene.
abstract: We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.
authors.affiliation: Department of Internal Medicine, Istituto di Medicina Interna e Geriatria, Policlinico Paolo Giaccone, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
authors.forename: C M
authors.initials: CM
authors.lastname: Barbagallo
authors.forename: G
authors.initials: G
authors.lastname: Emmanuele
authors.forename: A B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: B
authors.initials: B
authors.lastname: Fiore
authors.forename: D
authors.initials: D
authors.lastname: Noto
authors.forename: M C
authors.initials: MC
authors.lastname: Mazzarino
authors.forename: A
authors.initials: A
authors.lastname: Pace
authors.forename: A
authors.initials: A
authors.lastname: Brogna
authors.forename: M
authors.initials: M
authors.lastname: Rizzo
authors.forename: A
authors.initials: A
authors.lastname: Corsini
authors.forename: A
authors.initials: A
authors.lastname: Notarbartolo
authors.forename: S
authors.initials: S
authors.lastname: Travali
authors.forename: M R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005808:Genes, Recessive / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D012333:RNA, Messenger / Q000032:analysis; D018570:Risk Assessment; D035781:Siblings; D012802:Sicily; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000960:Hypolipidemic Agents; C469745:LDLRAP1 protein, human; D012333:RNA, Messenger