| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Tadayuki 国立療養所, 東埼玉病院, 副院長
SUNOHARA Nobuhiko 国立精神, 神経センター神経研究所・疾病研究第一部, 併任研究員
HAYASHI Yukiko 国立精神, 神経センター神経研究所・疾病研究第一部, 流動研究員
TSUKAHARA Toshifumi 国立精神, 神経センター神経研究所・疾病研究第一部, 研究員 (60207339)
TAKEDA Shinichi 国立精神, 神経センター神経研究所・疾病研究第一部, 室長 (90171644)
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| Research Abstract |
There have been great advances in molecular genetic diagnosis of muscular dystrophies in recent years which in turn produces a valuable implications for both genetic counseling and the elucidation of the etiology of the disease. Since molecular diagnoses are independent of the patient's age, they provide with an useful information before any clinical symptoms appear. At the genetic level, DNA and RNA-based molecular diagnosis and linkage analysis were performed. Isolation of the gene(s) permitted us the direct identification of mutations using standard Southern bloc, Northern blot, PCR or RT-PCR techniques. We also used a PCR assay to study X inactivation. At the biochemical level, protein-based molecular diagnosis of the diseases could also be done by both immunoblotting and immunocytochemistry.
X-linked dystrophinopathy is the commonest cause of muscular dystrophy. The high frequency of isolated male Dunchenne patients (^-30%) implies that there are also isolated female dystrophinopat
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hy patients including Duchenne muscular dystophy (DMD) carrier. of the 3,048 diagnostic biopsies processed over 12 years to our Institute, 41 cases carried the clinical diagnosis of limbgirdle muscular dystrophy(LGD) and 4 cases carried quadriceps myopathy(QM). We found 17% of out LGD and 4 cases carried quadriceps myopathy(QM). We found 17% of our LGD patients to be a dystrophinopathy, indicating that they in fact had a disorder related to DMD/BMD.Misclassification of isolated male LGD patients was 31%(4/13), while misclassification of isolated female LGD patients was 13%(2/15). All 4 patients with QM had clear abnormalities of dystrophin. Our study emphasizes the clinical overlap between LGD, QM and dystrophinopathy, and reinforces the necessity of dystrophin protein and gene studies for the accurate diagnosis of isolated cases of muscular dystrophy. Multiplex PCR analysis of the DMD gene revealed that 60-80% of DMD/BMD patients had deletions of the gene. We have accomplished a total of 1,116 DNA samples.
Facioscapulohumeral muscular dystrophy (FSHD) and myotonic dystrophy (MD) are autosomal dominant PMD, and both show highly variable clinical phenotypes from almost normal (abortive) to severe forms. Application of a chromosome 4q35-qter markers, P13E-11 (D4S810) and out own pFR-1, for the detection of DNA rearrangement in Japanese population and for the diagnosis of FSHD, and chromosome 19q13 marker, pM10M6, for the detection of the unstable triplet (CTG) repeat in MD have also been accomplished. Less
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