Barbagallo C M, Emmanuele G, Cefalù A B, Fiore B, Noto D, Mazzarino M C, Pace A, Brogna A, Rizzo M, Corsini A, Notarbartolo A, Travali S, Averna M R
Department of Internal Medicine, Istituto di Medicina Interna e Geriatria, Policlinico Paolo Giaccone, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
Atherosclerosis. 2003 Feb;166(2):395-400. doi: 10.1016/s0021-9150(02)00379-9.
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.
我们描述了一个西西里岛家族，该家族呈现出一种隐性高胆固醇血症形式，携带常染色体隐性高胆固醇血症（ARH）基因突变。在三个同胞中的两个，即一名26岁男性和一名22岁女性中，诊断出严重高胆固醇血症，血浆胆固醇水平非常高（分别为15.9和12.2 mmol/L）；存在腱黄瘤和睑黄瘤，并且在男性先证者中记录到弥漫性冠状动脉粥样硬化疾病，进展迅速且致命。父母双方的血浆胆固醇水平正常或略有升高。排除了继发性高胆固醇血症的所有病因以及低密度脂蛋白受体或载脂蛋白B基因的参与。β-谷甾醇血浆水平在正常范围内。对父母和两名先证者进行皮肤活检所获得的培养成纤维细胞显示出结合和降解125I-低密度脂蛋白的正常能力。对ARH基因进行直接测序表明，两名先证者均存在纯合子432insA突变；父母是该相同突变的杂合子。此突变是西西里岛ARH基因导致隐性高胆固醇血症形式的首次突变报告。
