眼咽型肌营养不良病理及分子遗传学研究

Pathological and molecular genetic studies on oculopharyngeal muscular dystrophy

目的研究眼咽肌营养不良(ocu lopharyngeal muscu lar dystrophy,OPMD)的遗传学和病理形态学表现。方法应用透射电镜技术对6例患者提上睑肌进行超微结构观察和分析,并采用聚合酶链反应(PCR)产物直接测序法对来自3个家系的OPMD患者11例及其亲属共27名外周血进行检测。结果4例患者眼肌活检标本于电镜下可观察到特异性核内包涵体(intranuc lear inc lusions,INIs),在细胞核内出现率分别为18%、20%、34%及40%。而9例患者基因中存在(GCG)6重复序列拷贝数异常(GCG)8、(GCG)10,亲属中未发病者均未见重复序列的异常扩增。结论OPMD患者受累眼肌活组织检查于电镜下可见INIs,并且INIs出现比率与异常扩增数目成正比。OPMD患者存在(GCG)6重复序列的异常扩增,并且发病年龄与异常扩增数目成反比。

Objective To study the pathologic and molecular genetic characteristics of Chinese patients with oculopharyngeal muscular dystrophy （OPMD）. Methods The ultrastructural muscle biopsies in 6 patients were carried out by using transmission electron microscopy. The DNA was obtained through blood samples from patients （n=11） and the at-risk individuals （n=16）. Amplification of the PABPN1 gene mutation region was performed by polymerase chain reaction （PCR）. The sequences were obtained and compared with the genomic sequence of the human PABPN1 gene. Results Intranuclear inclusions （INIs） were found by electron microscopy in 4 patients, and the rate of appearance was 18% , 20% , 34% and 40%. Sequence analysis of exon 1 of PABPN1 gene showed abnormal expansions of the GCG-repeat-（GCG） s and （GCG）10 in 9 patients. Conclusions INIs might be found by electron microscopy in muscle biopsies of OPMD patients. The rate of appearance of INIs should have positive relationship with the amount of the GCG-repeat. PABPN1 gene mutations might be present among Chinese patients with OPMD, and should have a negative relationship with the age of onset.