Molecular analysis of the inherited metabolic diseases---Mucopolysaccharidoses, Mitochondrial acetoacetyl-CoA thiolase deficiency and Peroxisomal diseases--

1.在MPSII IVA和VII患者中的几个突变已被首次鉴定。已确定GALNS基因的基因组结构。与Sly教授的小组合作并广泛地进行了MPSVII患者的分子分析，并鉴定了12种不同的突变。国际合作研究提供了近100例MPSIVA患者，共发现45种不同类型的突变，特别是日本人常见的双基因缺失和高加索人常见的错义突变。2.对21例患者进行了β-酮硫解酶缺乏症的分子基础分析。我们将在一篇综述文章《突变更新》中报告13例患者的17种突变和发现。我们发现了外显子突变导致外显子跳跃的现象，结果发表在J.Clin.Invest.上。其他的发现在2004年的三篇论文中报道。穆塔还有一篇发表在《产前诊断》上的论文用抗人胞浆型乙酰辅酶A硫解酶抗体克隆了人胞浆型乙酰辅酶A硫解酶的cDNA，并在BBRC中进行了序列分析。在肾上腺脑白质营养不良患者中发现了几个基因突变。F组Zellweger综合征的致病基因PAF-1定位于8 q21。C组Zellweger综合征的候选基因最近被克隆。

1.Several mutations in MPSII IVA and VII patients have first identified. The genomic structure for GALNS gene has been determined. Molecular analysis of MPSVII patients were performed cooperatively and extensively with prof. Sly's group and 12 different mutations were identified. Nearly 100 MPSIVA patients were supplied by international cooperative study, 45 various kinds of mutations have been defined ; especialy common double gene deletion found on Japanese ancestry and common missense mutation in Caucasian ancestry were noted.2.Molecular basis of beta-ketothiolase deficiency has been analyzed in 21 patients. We will report 17 mutations and findings in 13 patients in Mutation Update, a areview article. We discovered a phenomenon that an exonic mutatioon caused the exon skipping and the result was published in J.Clin.Invest..Other findngs were reported in three papers in Hum. Mutat. and a paper in Prenatal Diagnosis. We also cloned human cDNA for cytosolic acetoacetyl-CoA thiolase with anti-human cytosolic thiolase antibody and publishied it in BBRC.3.cDAN for human peroxisomal acyl-CoA oxidase was cloned and pathogenic gene mutation was identified in siblings with acyl-CoA oxidase deficiency. Several gene nutations were identified in patients with adrenoleukodystrophy. Chromosomal localization of PAF-1, the pathogenic gene for group F Zellweger syndrome, was determined to be 8q21.1 Gene mutations were identified in 3 group F patients. A candidate gene for group C Zellweger syndrome has been cloned recently.