一个Usher综合征2型家系USH2A基因的突变分析

Identification of novel compound heterozygous mutations of USH2A gene in a family with Usher syndrome type Ⅱ

目的 鉴定1个Usher综合征2型家系USH2A基因的致病性突变,为其提供分子遗传学依据.方法 对1个Usher综合征家系2例患者与4名表型正常家系成员的USH2A基因的全部编码区及侧翼剪切位点进行PCR扩增,产物直接测序进行突变分析,同时选择100名无亲缘关系的正常对照进行检测.结果 家系中2例患者（先证者及其妹妹）均携带了USH2A基因第42外显子c.8272G＞T（p.E2758X）和第63外显子c.12376-12378 ACT＞TAA（p.T4126X）复合杂合性突变.而患者的父亲为c.12376-12378 ACT＞TAA杂合突变携带者,其母亲为c.8272G＞T杂合突变携带者,两名表型正常的家系成员未检测到突变.经检索HGMD数据库两个突变均为新突变,且与家系疾病表型共分离.100名无血缘关系的正常人中未发现该突变.结论 USH2A基因的c.8272G＞T（p.E2758X）和c.1237612378ACT＞TAA（p.T4126X）复合杂合性突变可能为该家系的致病原因,为该Usher综合征家系的病因诊断提供了分子遗传学依据.

Objective To identify potential mutations in a Chinese family with Usher syndrome type Ⅱ.Methods Genomic DNA was obtained from two affected and four unaffected members of the family and subjected to amplification of the entire coding sequence and splicing sites of USH2A gene.Mutation detection was conducted by direct sequencing of the PCR products.A total of 100 normal unrelated individuals were used as controls.Results The patients were identified to be a compound heterozygote for two mutations：c.8272G〉T （p.E2758X） in exon 42 from his mother and c.12376-12378ACT〉TAA （p.T4126X） in exon 63 of the USH2A gene from his father.Both mutations were not found in either of the two unaffected family members or 100 unrelated controls,and had completely co segregated with the disease phenotype in the family.Neither mutation has been reported in the HGMD database.Conclusion The novel compound heterozygous mutations c.8272G〉T and c.12376-12378ACT〉TAA within the USH2A gene may be responsible for the disease.This result may provide new clues for molecular diagnosis of this disease.