| Project/Area Number |
18591141
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
HAYASAKA Kiyoshi Yamagata University, School of Medicine, Professor (20142961)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SASAKI Ayako Yamagata University, School of Medicine, Assistant Professor (60333960)
ODAGIRI Tesshu Yamagata University, School of Medicine, Assistant professor (30400550)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Charcot-Marie-Tooth disease / hereditary neuropath / DHPLC / MLPA / CMT1A / 髄鞘 / 遺伝子欠失 / 抹消神経 / MLPA / PRX / Nav1.6 |
|---|
| Research Abstract |
Charcot-Marie-Tooth disease (CMT) is a most common hereditary neuropathy and is a genetically heterogeneous disease. Many responsible genes have been identified, however, disease-causing mutations had not been identified in many Japanese patients. So we established denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) methods for screening of major disease-causing genes. We studied many Japanese patients with no CMT1A duplication and detected 15 cases with MPZ mutations, 18 cases with GJB1 mutations, 6 cases with PMP22, 1 case with EGR2 mutations and 4 cases with PRX mutations in demyelinating CMT using DHPLC method. As for axonal CMT, DHPLC screening detected 3 cases with MPZ mutations, 2 cases with GJB1 mutations and 10 cases with MFN2 mutations. In addition, DHPLC screening detected 2 cases with HSP27 mutations in distal hereditary motor neuropathy. MLPA screening did not detect a change in gene copy numbers except for CMT1A (PMP22) duplication. Nine cases were found to have CMT1A duplications and 3 of them had not been found by Southern blot hybridization or FISH methods. Our study confirmed that a change in gene copy numbers except for PMP22 is not a cause of CMT and MLPA is more sensitive to detect CMT1A duplication than Southern blot hybridization or FISH methods.
|
