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

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。

Clinical and genetic study of autosomal dominant congenital nystagmus family

Objective To study the clinical phenotype in a Chinese family with congenital nystagmus and deternune the disease-causing mutation. Methods A detailed clinical ophthalmic and complete physical examinations were performed for all patients in the congenital nystagmus fanuly. 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 fanuly was jerk nystagmus with null-point. OnIy 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.