细丝蛋白C肌病基因存在新的插入缺失突变

Filaminopathy caused by a novel deletion-insertion mutation in filamin C gene

目的报道在1个细丝蛋白C（filaminC，FLNC）肌病家系中发现的新的插入缺失突变。方法该家系连续5代共有19例患者，临床和病理资料在前期研究中已经作为肌原纤维肌病进行了报道。现对包括先证者在内的3例患者、5名无症状家系成员和50名健康人进行FLNC基因的测序，利用质粒将FLNC基因的第18号外显子扩增产物进行克隆分离，然后进行电泳鉴定和直接测序。结果先证者的FLNC基因的第18号外显子存在18个正常碱基缺失，同时插入6个异常碱基，导致FLNC蛋白第7个免疫球蛋白样杆状重叠结构异常，继而致FLNC蛋白结构的失稳。家系中另2例患者存在同样的突变，而5名无症状家系成员和50名健康对照均正常。结论FLNC肌病存在FLNC基因第18号外显子新的插入缺失突变，我们发现该病可以出现在德国之外的其他种族。

Objective To report filaminopathy witb novel insertion mutation in a Chinese family. Methods Total 19 patients from successive 5 generations involved in an autosomal dominant family. The detailed clinical manifestations had been described （Chinese Journal of Neurology, 2008, 41：751-755 ）. The filamin C gene sequencing was performed in 3 patients, 5 family members without symptoms and 50 normal persons. The amplified fragments of the exon 18 in filamin C gene were cloned into pBluesripts vectors, then sequenced and identified with capillary electrophoresis. Results 18-nucleotide deletion and 6-nucleotide insertion were identified in the exon 18 of filamin C gene. The mutation caused the disturbance of the seventh immunoglobulin-like domain in filamin C, leading to the instability of dimmers of filamin C. Another 2 patients in the family had same mutation while 5 family members without symptoms and 50 normal controls were normal. Conclusion The novel nucleotide deletion-insertion in exon 18 of filamin C gene causes filaminopathy. This disease can appear in non-Nordic race.