土家族中一个先天性无虹膜家系的临床特点和PAX6基因突变位点分析

目的：确认土家族中一个先天性无虹膜家系的PAX6基因致病突变并分析其临床特点。方法：实验研究。详细询问家族病史并对该家系中所有7 例成员（4 例患者，3 例正常人）进行详细的眼部检查，采集家系成员及100例（50例土家族人和50例汉族人）正常对照者的外周静脉血，提取DNA；对先证者PAX6基因的全部外显子进行PCR扩增及测序；对家系中所有成员和正常对照者进行PAX6基因突变位点的验证检测。结果：该家系中患者主要以虹膜缺损、白内障、眼球震颤、黄斑中心凹发育不良和角膜病变为主要临床表现，虹膜缺损轻重不一，角膜病变和白内障情况随年龄增加而加重。该家系的4 例患者均在第3 外显子与内含子3 交界处出现一个杂合突变（c.357+1G > A），正常家系成员及正常对照者均无此突变。结论：该先天性无虹膜家系患者虹膜缺损程度不一。PAX6是该家系的致病基因，该家系患者PAX6基因的突变位点是杂合突变(c.357+1G > A）。

Analysis of the PAX6 Gene Mutation and Clinical Characteristics in a Chinese Tujia Family with Congenital Aniridia

Objective: To observe the clinical characteristics and identify a potential mutation of the PAX6 gene responsible for congenital aniridia in a Chinese Tujia family in central China. Methods: In this experimental study, data from a detailed family history and ophthalmologic examinations were collected. Genomic DNA was extracted from the peripheral blood of seven family members and 100 healthy individuals (50 Tujia and 50 Han nationalities). The coding regions and flanking sequence of the PAX6 gene of the propositus members were amplified by PCR and subjected to DNA sequencing. The genetic sequence of the mutant site of the unaffected family members and control group's individuals were verified. Results:The clinical characteristics of the affected family members with iris hypoplasia with or without cataract,nystagmus, foveal dysplasia or keratopathy were analyzed. Cataract and keratopathy were aggravated with age. A heterozygous mutation (c.357+1G > A) was identified at the junction of exon 3 and intron 3 in four patients but not in the unaffected family members or 100 healthy individuals. Conclusions: The degree of iris hypoplasia is variable. The c.357+1G > A heterozygous mutation of PAX6 is found to underlie the aniridia in an autosomal dominant inheritance manner.