MOLECULAR GENETICS OF CHOLESTEROL METABOLIC PATHWAY AND TREATMENT OF ATHEROSCLEEROSIS

家族性高胆固醇血症的LDL受体异常：全世界已报道LDL受体基因有600多种不同的突变。我们收集了20个FH纯合子和1，500多个FH杂合子。本实验室已鉴定出11种LDL受体基因变异体。LDL受体基因K790X突变是本地区常见的突变型，在FH患者中的频率为20.9%。这11种突变仅占FH的38.8%，其余61.2%的FH中LDL受体基因突变尚不清楚。基因分析显示第10外显子和第9内含子连接处的点突变（G至A），这将产生剪接异常，并且没有MTP蛋白。先证者在染色体4q上只有他母亲的基因。母亲同二体是该患者MTP基因突变纯合性的基础。丹吉尔病中的ABC 1突变丹吉尔病是一种罕见的疾病，其特征是高密度脂蛋白胆固醇水平非常低，橙色扁桃体肥大，动脉粥样硬化和脊髓神经病。在日本报告的丹吉尔病患者不到10例。1999年，ABC1突变被发现是丹吉尔病的致病基因突变。我们在我们的三个Tangie病中发现了三个新的ABC1基因突变。突变均为外显子18的A2743C和N875H突变。

LDL-RECEPTOR ABNORMALITIES IN FAMILIAL HYPERCHOLESTEROLEMIA.More than 600 different mutations in the LDL receptor gene have been reported in the world. We have collected 20 homozygotes and more than 1,500 heterozygotes of FH. Eleven variants of LDL receptor gene have been identified in our laboratory. K790X mutant of LDL-receptor gene was a common mutant in this district, and the frequency was 20,9% in FH patients. These 11 mutants accounted for only 38.8% of FH and in other 61.2% of FH the LDL receptor gene mutants remained unknown.MICROSOMAL TRANSFER PROTEIN (MTP) GENE MUTATION IN ABETALIPOPROTEINEMIA.The proband was 29 male patient, and his CHOL level was 33 mg/dl, TG was 0 mg/dl, and HDL-C was 28 mg/dl. The gene analysis showed a point mutation in the junction of exon 10 and intron 9 (G to A), which would produce splicing abnormalities and no MTP protein. The proband had only his mother's genes in chromosome 4q. Maternal isodisomy was the basis for homozygosity of the MTP gene mutatin in this patient.ABC1 MUTATION IN TANGIE'S DISEASE.Tangier's disease is a rare disease characterized by very low levels of HDL-cholesterol, hypertrophy of orange-coloured tonsils, atherosclerosis and poluneuropathy. Less than 10 patients of Tangier's disease have been reported in Japan. In 1999, ABC1 mutations have been found to be a causative gene mutation in Tangier's disease. We found three novel mutations of ABC1 gene in our three Tangie's disease. Their mutation were A2743C and N875H mutation in exon 18.