2004 Fiscal Year Final Research Report Summary
Clinical and molceulcar analyses of facioscpubhumeral muscular dystrophy
| Project/Area Number |
15590922
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | National Institute of Neuroscience, National Center of Neurology and Psychiatry |
|---|
Principal Investigator |
HAYASHI Yukiko National Institute of Neuroscience, National Center of Neurology and Psychiatry, Dep.of Neuromuscular Research, Section Chief, 疾病研究第一部, 室長 (50238135)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHINO Ichiro National Institute of Neuroscience, National Center of Neurology and Psychiatry, Director, 疾病研究第一部, 部長 (00332388)
GOTO Kanako (後藤 加奈子) National Institute of Neuroscience, National Center of Neurology and Psychiatry, Researcher, 疾病研究第一部, 研究員 (00392415)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Muscular dystrophy / Autosomal Dominant / Gene deletion / Chromosome 4q35 / Somatic mosaicism / Molecular Diagnosiis / Clinical variability / Genetic variability |
|---|
| Research Abstract |
Facioscapulohumeral muscular dystrophy(FSHD) is a common muscular disorder with autosomal dominant inheritance. Most of the patients have a deletion of numbers of D4Z4 repeats on chromosome 4q35.
Somatic/germline mosaicism of the D4Z4 repeated region is suggested to cause de novo patients with FSHD in the next generation. We performed southern blot analysis on the FSHD patients and their parents, and revealed that about 20% of the parents were somatic mosaic. There was no difference between the ratio of the cells with deleted allele and the age at onset/clinical severity. Surprisingly, nearly a half of the parents with a deleted allele showed no clinical symptoms, which suggest much more low penetration of this disease than previously thought (Goto et al.,2004).
Clinical features of FSHD are quite variable even within a family. We analyzed in detail on 40 patients with 4q35-unlinked FSHD, based on our original clinical database for FSHD. We reported that FSHD contains clinically and genetically variable disorders, and other diseases such as Becker muscular dystrophy could show quite similar clinical features to FSHD (Yamanaka et al.,2004).
For the several reasons, genetic diagnosis of FSHD using southern blotting is quite complicate, and to develop a simple method is needed. We developed a new method for the molecular diagnosis of FSHD by using long PCR method. We confirmed that 95% of 4q35-linked FSHD patients can be diagnosed to detect a PCR product corresponding to the number of D4Z4 (paper submitted).
|
