一个先天性特发性眼球震颤家系中致病基因FRMD7的突变研究  

The G990T mutation of the FRMD7 gene in a Chinese family with congenital idiopathic nystagmus

作　　者：李宁东[1] 崔丽红[2] 王黎明[1] 马惠芝[1] 张丽玲[3] 岳以英[1] 赵堪兴[2] 

机构地区：[1]天津市眼科医院眼科分子遗传室,300020 [2]天津医科大学 [3]西安市儿童医院眼科

出　　处：《中华医学遗传学杂志》2008年第1期11-14,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（30070805）

摘　　要：目的研究一个先天性特发性眼球震颤家系的致病基因。方法选取X染色体上微卫星标记物，通过PCR扩增后，进行基因组扫描。应用GeneMapper软件进行PCR扩增产物片段大小和单倍型分析，Linkage5．1软件进行两点汉连锁值（Log of odds，LOD）计算，通过基因序列分析发现致病基因突变。结果经两点法计算，在DXS1047可获最大LOD值为8．55；基因序列分析发现FRMD7基因第9外显子存在G990T的杂合性基因突变。结论FRMD7基因突变是导致该家系出现疾病的主要原因。Objective To study the mutation of FRMD7 gene in a Chinese family with congenital idiopathic nystagmus. Methods Forty-six individuals in the Chinese family with congenital idiopathic nystagmus, including 16 patients, 19 nomml siblings and 11 spouses, were investigated under informed consent. Genomic DNA of all 46 members was isolated by standard protocol. The X-linked inherited pattern was ascertained by investigating the history of the family members and the clinical feature of each individual. The genome scan on X chromosome was performed after PCR ampli- fication for microsatellite markers. LOD scores were calculated with Linkage 5.1. Direct DNA sequence analysis was carried out to find the gene mutation responsible for the disease. Results A maximum LOD score of 8.55 （θ = 0） was obtained with polymorphic marker DXS1047. Haplotype construction of the family defined the disease interval between DXS8059 and DXS8033. Direct DNA sequence analysis revealed a heterozygous mutation of G990T in exon 9 of the FRMD7 gene in all patients, which was not present in unaffected family members. Conclusion Congenital nystagmus is a clinically and genetically heterogeneous ocular movement disease. The mutation of G990T of the FRMD7 gene is the underlying molecular pathogenesis for this family with congenital nystagmus.

关 键 词：先天性眼球震颤 FRMD7基因 突变 

分 类 号：R777.4[医药卫生—眼科]