常染色体显性遗传眼球震颤家系的临床表型及致病基因的研究  

Clinical and genetic study of autosomal dominant congenital nystagmus family

作　　者：布娟[1] 刘敬[1] 李爱军[1] 陆遥[1] 庞宏蕾[1] 刘峰[1] 王乐今[1] 

机构地区：[1]北京大学第三医院眼科,北京市100191

出　　处：《眼科新进展》2014年第11期1042-1044,共3页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:81300789)~~

摘　　要：目的研究1个中国人常染色体显性遗传性眼球震颤家系的临床特点,并通过候选基因直接测序的方法对该家系的致病基因及发病机制进行研究。方法选择1个先天性眼球震颤家系,对家系所有成员进行全身检查及视力、眼位、眼球运动、眼球震颤中间带、验光等眼科的相关检查后,从家系中每一代各选1例患者(包括先证者)及正常人,进行候选基因FRMD7、GPR143与PAX6基因的外显子测序。结果家系患者的眼球震颤为水平冲动型,并且具有中间带。除了先证者有部分眼组织缺损及小眼球等异常外,其余患者的眼前节均未见明显发育异常。家系患者PAX6基因第7外显子的第382碱基发生了杂合突变(c.C382T),从而引起了氨基酸的改变(p.R128C),该突变可能影响了PAX6蛋白与其调控的下游基因的调控序列的结合,进而导致PAX6基因功能异常,影响眼部发育。结论该常染色体显性遗传性眼球震颤家系的致病基因为PAX6基因。Objective To study the clinical phenotype in a Chinese family with congenital nystagmus and determine the disease-causing mutation. Methods A detailed clinical ophthalmic and complete physical examinations were performed for all patients in the congenital nystagmus family. Mutations in PAX6,FRMD7 and GPR143 were determined by PCR-based DNA sequencing assays and multiplex PCR assays for deletions. Results The affected members in the pedigree had classical phenotype of nystagmus. The type of nystagmus in the family was jerk nystagmus with null-point. Only the proband had ocular coloboma and congenital cataract. The missense mutation R128C（ caused by a 382 C→T heterozygous change） in PAX6 was identified in the Chinese congenital nystagmus family. The mutation was associated with the disease phenotype in patients,but not detected in their relatives or in the 100 normal controls. Conclusion The missense mutation of PAX6 is the molecular basis for the congenital nystagmus family.

关 键 词：先天性眼球震颤 常染色体显性遗传 PAX6基因 FRMD7基因 GPR143基因 

分 类 号：R774.1[医药卫生—眼科]