2007 Fiscal Year Final Research Report Summary
The development of faster genetic diagnosis of an inborn error of metabolism causing rhabdomyolysis and acute renal
| Project/Area Number |
18590918
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
KANEOKA Hidetoshi Fukuoka University, Facutly of Medicine, Professor (20161169)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takao Fukuoka University, Faculty of Medicine, Professor (10125552)
MUKAINO Yoshito Fukuoka University, Faculty of Sports and Health Science, Professor (40144266)
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| Project Period (FY) |
2006 – 2007
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| Keywords | genetic diagnosis / long-chained fatty acid / CPT II enzyme / rhabdomyolysis / acute renal failure / sequencing / denaturing HPLC / crystallography |
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| Research Abstract |
We could summarize our data into the following three points.
1) Genetic mutations of Japanese patients with carnitine palmitoyltransferase (CPT) II deficiency
We 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 gene
We 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 gene
For 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.
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