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Molecular cytogenetic study of the Fukuyama-type muscular dystrophy caused by the aberration of the untranslated region of the gene(FCMD)

基因非翻译区畸变引起的福山型肌营养不良症（FCMD）的分子细胞遗传学研究

基本信息

批准号：
11670612
负责人：
SAITO Fumiko
金额：
$ 2.24万
依托单位：
Tokyo Medical & Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670612/
关键词：
Fukuyama-type muscular dystrophy the untranslated region of the gene ISH method mRNA metabolism

项目摘要

Fukuyama-type congenital muscular dystrophy(FCMD)is an autosomal recessive disease in Japan(incidence is 0.7-1.2 per 10,000 births). Though Prof.Toda(co-investigator)et al.had recently identified a retro-transposal insertion of tandem repeats in the 3' untranslated region(UTR)of FCMD gene at 9q31(the founder haplotype)in the patients, the molecular mechanism of the causing disease has been still unknown. In this research project, we have succeeded in the detection of the transcript of FCMD within the nucleus by the method of in istu hybridization(ISH), and performed the two-color ISH method using various DNA clones investigate the dynamism of mRNAs in the cell nucleus of the patients. The results showed that the level of the transcripts of FCMD in the patients was very low(〜20%)in comparison with the normal individuals, which confirm the result of the molecular study by the co-investigator, which indicate that FCMD patients have the abnormality of the mRNA metabolism and mRNA of the mutant allele is transcribed but low or the stability of the transcript was low. As this may provide a key point to study the pathogenesis of the disease, we will make a further study to resolve the problem.

福山型先天性肌营养不良症(FCMD)是日本的一种常染色体隐性遗传病(发病率为0.7-1.2‰)。尽管Toda教授(合作者)等人最近在FCMD基因的9q31(创始人单倍型)的3‘非翻译区(UTR)上发现了串联重复序列的逆转录转座插入，但其致病的分子机制仍不清楚。在本研究项目中，我们成功地用原位杂交(ISU)的方法检测了FCMD在细胞核内的转录本，并用不同的DNA克隆进行了双色ISH方法，研究了患者细胞核内mRNAs的动态变化。结果显示，FCMD患者的FCMD转录本水平很低(~20%)，这与协作人的分子研究结果相一致，说明FCMD患者存在基因代谢异常，突变等位基因的mRNA转录水平较低或转录本稳定性较差。由于这可能为研究该病的发病机制提供一个关键点，我们将进一步研究以解决这一问题。