Objective To identify the pathogenic cause of familial congenital aniridia by mutation screening of the paired box 6 (PAX6) gene. Methods All participants in this experimental study, including the available family members of the recruited family and 100 unrelated healthy controls, received comprehensive ophthalmic examinations. Genomic DNA was extracted from peripheral blood. Mutation screening of 11 coding exons (exon 4 through exon 14) of PAX6 and the adjacent splicing junctions was performed by Sanger sequencing. Co-segregation analysis for the available family members and the normal controls were conducted later. Results A novel heterozygous deletion/insertion mutation c.569_570delinsACGG (p.Ile190Asnfs*18) in exon 8 of PAX6 was identified in the congenital aniridia family. This mutation consistently co-segregated with the affected family members and was not detected in the normal family members or in the 100 normal controls. Three in eight family members were diagnosed with congenital aniridia by comprehensive eye examinations. The patients with aniridia also had complications with heterogenic ocular manifestations, including keratopathy, different types of cataracts, macular dysplasia, mild ptosis, and mild horizontal nystagmus. Conclusion A novel PAX6 deletion/insertion mutation c.569_570delinsACGG (p.Ile190Asnfs*18) in exon 8 was the pathogenic mutation of the family and was associated with congenital aniridia. The finding expands the mutation spectrum of PAX6 in congenital aniridia.%目的 对中国一先天性无虹膜家系进行PAX6基因突变检测,以确定其突变位点.方法实验研究.收集一先天性无虹膜家系,采集该家系患者及健康成员的外周静脉血,收集100名健康人外周血作为正常对照,采用Sanger测序的方法对PAX6基因的11个外显子(外显子4-14)以及外显子-内含子连接区域进行测序,随后进行家系共分离分析以及正常样本的对照分析.结果该家系8名成员经全面眼科检查,3名确诊为先天性无虹膜,且合并有复杂的眼部表型,包括不同程度的角膜病变、不同类型的白内障、黄斑发育不良、轻度上睑下垂和轻度眼球水平震颤等.在该家系患者中发现一个新杂合突变[c.569_570delinsACGG(p.Ile190Asnfs*18)],该突变可致PAX6基因编码的蛋白截短,该突变符合共分离且在100名正常对照者中未检测到.结论PAX6基因第8外显子上一个新的杂合突变[c.569_570delinsACGG(p.Ile190Asnfs*18)]为本研究中先天性无虹膜家系的致病突变,该突变与先天性无虹膜有关,本研究扩大了PAX6基因的突变频谱.
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