先天性眼外肌纤维化ARIX基因多态性研究

ARIX gene polymorphism in patients with congenital fibrosis of extraocular muscles

目的分析两个先天性眼外肌纤维化(congenital fibrosis of theextraocular mus-cles,CFEOM)家系的临床表型,探讨家系ARIX基因多态性及其意义。方法对两个CFEOM家系中所有成员共13人进行详细的临床检查,确定患者和正常人。提取DNA,进行PCR扩增,扩增产物进行纯化、DNA测序鉴定,测序结果与GenBank中人ARIX基因序列进行同源性比较。结果两个家系的遗传方式均是常染色体隐性遗传,两个家系中共8例患者均表现为典型的CFEOM特征。家系Ⅰ中3例患者均在ARIX基因外显子1出现同义突变156C>T,在外显子2出现116G>A,也为同义突变;家系Ⅱ中5例患者在ARIX基因外显子2发生两处突变,即21G>A和116G>A,其中116G>A为同义突变;两家系中正常人均无上述改变。结论此两家系均属于CFEOM2型,ARIX基因突变可能是导致该两家系致病的分子基础。

Objective To describe the clinical phenotype in two Chinese family with congenital fibrosis of the extraocular muscles（CFEOM）,and investigate the ARIX gene polymorphism in the families and its significance.Methods The detailed clinical ophthalmic examination was performed for all 13 patients with CFEOM in two Chinese families,confirmed the patients and healthy controls.The genomic DNA of all family members was extracted from peripheral blood leukocytes and amplified with PCR.The PCR products were purified for DNA sequencing.DNA sequences were aligned with the human ARIX gene sequences registered in GenBank.Results The affected eight members in the two pedigrees had classic phenotype of CFEOM.They were inherited as an autosomal recessive trait.A 156CT synonymous mutation of exon 1 and a 116GA synonymous mutation of exon 2 appeared in three patients in pedigreeⅠ.A 21GA mutation and a 116GA synonymous mutation of exon 2 appeared in five patients in pedigree Ⅱ.The normal individuals in the two pedigrees had no above changes.Conclusion The disorder in the two families should be referred as CFEOM2,the gene ARIX mutation may be the molecular basis of pathopoiesis.