一个常染色体显性视网膜色素变性家系表型分析和RHO基因突变检测

Mutations of rhodopsin gene in a family with autosomal dominant retinitis pigmentosa

目的分析一常染色体显性视网膜色素变性(autosomal dominant retinitis pigmentosa,adRP)家系的临床表型,确定该家系与视紫红质(rhodopsin,RHO)基因的关系。方法依据RP诊断标准及患者临床表型,确定一连续4代发病的adRP家系遗传的特点;采集家系中13位成员外周血8-10ml,提取基因组DNA;聚合酶链反应(polymerase chain reaction,PCR)扩增RHO基因的第1-5外显子基因片段,产物纯化后直接测序;测序结果与美国国立生物技术信息中心(National Center forBiotechnology Information,NCBI)数据库上公布的核酸标准序列进行比对分析。结果该家系临床特点为所有患者均于10岁左右出现夜盲,1例22岁出现视野损害,2例40岁左右出现视野损害,并且于50岁左右双眼相继发生急性闭角型青光眼和并发性白内障。该家系5例患者在RHO基因外显子、上下游非编码序列以及内含子及外显子拼接部中均未发现碱基改变。结论本研究家系患者存在遗传异质性和表型异质性,RHO基因不是该家系的致病基因。

Objective To study the relation between a family with autosomal dominant retinitis pigmentosa（adRP） and rhodopsin （RHO） by analyzing the clinical phenotype of adRP. Methods Genetic characteristics of the family with adRP occurring in 4 consecutive generations were observed according to the RP diagnostic criteria of retinitis pigmentosa（RP） and the clinical phenotype of the adRP family members. Peripheral blood samples（8-10ml） were taken from 13 family members of the family with adRP. Genomic DNA was isolated and the first 5 exons of RHO gene segments were amplified by PCR. The purified PCR products were directly sequenced, which was compared with the standard sequence of nucleic acid from National Center for Biotechnology Information（NCBI）. Results Night blindness occurred in all members of the family at the age of about 10 years. Visual field damage was observed in 1 member at the age of 22 years and in 2 members at the age of 40 years who developed acute angle-closu re glaucoma and cataract at the age of about 50 years. No base change was found in RHO exons, non-downstream and upstream-coding sequence, and connection between intron and exon of RHO in 5 members. Conclusion Genetic and phenotypic heterogeneity is found in members of the family and RHO is not the pathogenic gene in the family.