一先天性无虹膜家系PAX6基因遗传筛查及临床表型

目的探讨我国常染色体显性遗传先天性无虹膜一家系患者的致病基因突变位点及其临床表型。方法实验研究。于南京医科大学第一附属医院眼科收集一先天性无虹膜家系，共8名家庭成员，其中3名患者，2名正常同胞，3名配偶。完善该家系内所有参与者的眼科检查，采集该家系成员的外周静脉血，提取基因组DNA，扩增PAX6基因的全部编码区及外显子-内含子交界区剪切位点附近的序列，直接测序法确定该家系的致病突变。结果遗传学筛查结果证实该家系的致病突变为位于PAX6基因第7号外显子与第7号内含子交接处的杂合突变（c.357+5G>A）。生物信息学分析结果表明该突变可导致正常剪切位点的缺失，产生移码突变，形成截短蛋白p.Ser121Asnfs*30。该家系中3例患者均表现出典型的先天性无虹膜症的临床表型，表现为虹膜发育不全，与此同时，该家系内患者还具有上睑下垂、白内障、眼球震颤、青光眼及玻璃体混浊等眼部异常。结论PAX6 c.357+5G>A杂合突变为该家系的致病突变，是该家系发生先天性无虹膜及上睑下垂、白内障、眼球震颤、青光眼及玻璃体混浊等一系列临床表型的主要致病原因。

A PAX6 gene mutation causes aniridia in a Chinese family

Objective To identify the disease causative mutation in a Chinese family with congenital aniridia and to characterize its clinical phenotypes.Methods This was a case series study.Eight participants were recruited from the index family,including 3 patients,2 asymptomatic siblings,and 3 spouses.All participants underwent detailed ophthalmic examinations.Peripheral blood samples were taken from all family members for DNA extraction.All coding and exon-intronic boundary regions of the PAX6 gene were amplified and sequenced to identify the disease causative mutation for this family.Results PAX6 c.357+5G＞A,a heterozygous mutation located at the boundary region of exon 7 and intron 7,was identified as the disease causative mutation for this family.Bioinformatics analysis indicated that this mutation would cause the elimination of the regular splice-site and generate the truncated protein p.Ser121Asnfs*30.All three patients in this family presented with iris hypoplasia.Patients were also associated with other ocular abnormalities,including ptosis,cataract,glaucoma,vitreous opacities,reduced visual acuity,and nystagmus.Conclusion A heterozygousmutation of PAX6 c.357+5G＞A causes aniridia and its associated ocular phenotypes,including ptosis,cataract,glaucoma,vitreous opacities,reduced visual acuity,and nystagmus,in the present family.