Insertional mutation by transposable element, L1, in the DMD gene results in X-linked dilated cardiomyopathy
Insertional mutation by transposable element, L1, in the DMD gene results in X-linked dilated cardiomyopathy
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DOI：
10.1093/hmg/7.7.1129
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发表时间：
1998-07-01
影响因子：
3.5
通讯作者：
Takeda, S
中科院分区：
文献类型：
--
作者：
Yoshida, K;Nakamura, A;Takeda, S
X-连锁扩张型心肌病(XLDCM)是一种以心肌损害为特征的临床表型，无明显的骨骼肌病临床症状，迄今已在XLDCM患者中发现了Duchenne肌营养不良基因DMD的几个突变，但DMD中的这些心脏特异性突变与XLDCM表型的致病相关性尚不清楚。我们在这里报告了来自两个不相关的日本家庭的三名XLDCM患者在DMD的肌肉外显子1中发现了一个独特的从头L1插入。该插入片段是人L1基因的5‘-截短型，反向整合在肌肉L外显子的5’-非翻译区，这可能是由于其独特的整合部位，影响了肌营养不良蛋白转录本的转录或稳定性，但不影响脑或浦肯野细胞的转录或稳定性。我们推测，DMD中L1序列的这种插入是导致部分日本XLDCM患者的原因。
X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt clinical signs of skeletal myopathy, To date, several mutations in the Duchenne muscular dystrophy gene, DMD, have been identified in patients with XLDCM, but a pathogenic correlation of these cardiospecific mutations in DMD with the XLDCM phenotype has remained to be elucidated. We report here the identification of a unique de novo L1 insertion in the muscle exon 1 in DMD in three XLDCM patients from two unrelated Japanese families. The insertion was a 5'-truncated form of human L1 inversely integrated in the 5'-untranslated region in the muscle exon l, which affected the transcription or the stability of the muscle form of dystrophin transcripts but not that of the brain or Purkinje cell form, probably due to its unique site of integration. We speculate that this insertion of an L1 sequence in DMD is responsible for some of the population of Japanese patients with XLDCM.