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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疾病（发病率为每10，000名新生儿0.7-1.2例）。虽然户田教授（合作研究者）等最近在患者中鉴定了FCMD基因9 q31（创始者单倍型）的3'非翻译区（UTR）中的串联重复序列的逆转录-转录插入，但引起疾病的分子机制仍然未知。本研究采用原位杂交（ISH）方法成功地检测了FCMD在细胞核内的转录本，并利用不同的DNA克隆进行了双色ISH方法，研究了患者细胞核内mRNA的动态变化。结果显示，FCMD患者的基因转录水平较正常人低（约20%），证实了合作研究者的分子生物学研究结果，即FCMD患者存在mRNA代谢异常，突变等位基因的mRNA转录水平低或转录稳定性低。这可能为研究该病的发病机制提供了一个关键点，我们将进一步研究以解决这一问题。