The development of faster genetic diagnosis of an inborn error of metabolism causing rhabdomyolysis and acute renal

我们可以将我们的数据归纳为以下三点。1)日本肉碱棕榈酰基转移酶（CPT） II缺乏症患者的基因突变我们利用pcr扩增基因产物的直接DNA测序分析了7例CPT II缺乏症患者。我们发现7例患者中有6例携带F383Y突变，纯合或杂合。我们从文献中收集了3例日本患者的遗传数据，也发现其中2例有F383Y。80%的CPT II缺乏症高加索患者有S113L和/或P50H突变。结合我们的研究结果，我们提出了CPT II缺乏症的种族特异性突变。最近大鼠CPT II分子的晶体学数据表明F383Y和S113L突变的重要性。2) CPT II基因的突变与多态性我们招募了50名健康志愿者，测定了他们的CPT II基因型。我们没有发现任何已知的致病突变或snp，但已知的三个。这三种SNP在我们组中所占的比例与预期一致，但SNP C352C在日本患者中的发病率增加，没有统计学上的证明。为了大规模筛选CPT II基因的突变和多态性，我们利用pcr扩增基因产物热变性高效液相色谱法（PCR-DHPLC）进行了CPT II基因的突变和多态性筛选。我们分析了50名志愿者的CPT II基因，并比较了直接DNA测序的数据。两种方法的结果具有良好的可比性，证明了PCR-DHPLC对CPT II基因的遗传大量筛选的有效性。

We could summarize our data into the following three points.1) Genetic mutations of Japanese patients with carnitine palmitoyltransferase (CPT) II deficiencyWe analyzed 7 patients with CPT II deficiency utilizing direct DNA sequencing on PCR-amplified gene products. We found six patients out of the seven carried F383Y mutation, homozygously or heterozygously. We collected genetic data of three Japanese patients from literatures and also found two of them had F383Y. Eighty % of Caucasian patients with CPT II deficiency have S113L and/or P50H mutations. Together with our findings, we propose the ethnic specific mutation of CPT II deficiency. Recent data of crystallography on a rat CPT II molecule suggests the importance of F383Y and S113L mutations.2) Mutations and polymorphisms of CPT II geneWe enrolled 50 healthy volunteers, and determined their genotypes of CPT II gene. We failed to find any known pathogenic mutation nor SNPs but known three. The proportion of the three SNPs among our group was as expected, however the incidence of SNP C352C was increased among Japanese patients, not being proved statistically.3) Mass-screening of mutations and polymorphisms of CPT II geneFor mass-screening of mutations and polymorphisms of CPT II gene, we utilized heat-denaturing high performance liquid chromatography of PCR-amplified gene product (PCR-DHPLC). We analyzed CPT II genes from the 50 volunteers, and compared the data of the direct DNA sequencing. The results were well comparable between two methods, which proved the usefulness of the PCR-DHPLC for the genetic mass-screening of CPT II gene.