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

福山型先天性肌营养不良症（FCMD）在日本是一种常染色体隐性遗传病（发病率为每10,000个新生儿0.7-1.2个）。虽然toda教授（共同研究者）等人最近在患者中发现了fmd基因9q31（创始单倍型）3'非翻译区（UTR）的串联重复序列的反转置插入，但致病的分子机制仍然未知。在本研究项目中，我们成功地用原位杂交（ISH）方法检测了口fcmd在细胞核内的转录本，并使用多种DNA克隆进行双色杂交（ISH）方法研究了患者细胞核内mrna的动态。结果显示，与正常人群相比，fmd患者的转录本水平非常低（~ 20%），这证实了共同研究者的分子研究结果，表明fmd患者存在mRNA代谢异常，突变等位基因的mRNA转录但较低或转录稳定性较低。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。

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.