【作者】 宋贵波； 严明； 杨国华； 郑芳；

【Author】 Song Guibo~1,Yan Ming~2,Guohua Yang~1,Zheng Fang~1 1 Center for Gene Diagnosis,Zhongnan Hospital,Wuhan University,Wuhan,430071; 2 Department of Ophthalmology,Zhongnan Hospital,Wuhan University,Wuhan,430071

【机构】 武汉大学中南医院基因诊断中心； 武汉大学中南医院眼科；

【摘要】 目的:在一常染色体显性遗传视网膜色素变性(autosomal dominant retinitispigmentosa,ADRP)的家系中筛查突变基因。方法 :应用PCR-DNA测序技术,对该家系的5名RP患者及7名正常人外周血DNA进行分子遗传学分析,筛查10个候选基因,包括RHO、RDS、ROM1、PRPF31、RP1、PRPF3、PRPF8、IMPDH1、CRX和NRL。结果 :测序结果发现该家系中4名患者和1名正常人的视网膜变性慢蛋白(peripherin 2/retinal degeneration slow,PRPH2/RDS)基因第一个外显子中第148位碱基发生了G→C的突变,此突变相应地导致了第50位氨基酸残基由Asp变成His(D50H),而家系中另1名患者和其他成员未携带此突变。通过对人类,牛,大鼠,小鼠的RDS蛋白进行比较,发现该氨基酸残基在不同物种间不是保守的。此外,对ROM1基因所有外显子及其剪接位点区域进行突变筛查,未发现突变。结论 :在该三代人的ADRP家系中发现了一个位于RDS基因上的D50H突变,但该突变与RP疾病未出现"共分离"现象;同时排除了RDS/ROM1双基因型突变的可能,因此错义突变D50H不是该ADRP家系的致病基因,系RDS基因的多态现象。更多还原

【Abstract】 Objective:To screen the gene mutation associated with autosomal dominant retinitis pigmentosa in a three generations Chinese family.Methods:Genomic DNA from five patients and seven normal persons in the ADRP pedigree were extracted.Subsequently,Known candidate genes for autosomal dominant retinitis pigmentosa such as RHO,RDS,ROM1,PRPF31,RP1,PRPF3, PRPF8,IMPDH1,CRX and NRL were analyzed by polymerase chain reaction(PCR) amplification followed by direct DNA sequencing.Results:Mutation screening identified one heterozygous G→C transversion at nucleotide 148 in the first exon of RDS gene,resulting in an amino acid change from aspartic acid to histidine at codon 50(D50H).This mutation was present in four affected family members and one unaffected person of the family,but it was absent in the rest one patient and other family members.Accroding to compare the RDS protein from human,cow,rat and mouse,we found the aspartic acid at codon 50 was not conserved in RDS genes,in different species. Furthermore,there were no mutations in the entire ROM1 coding region and flanking intron/exon junctions.Conclusions:This study identified a missense mutation D50H in RDS gene in a family with ADRR However,this mutation didn’t cosegregate with the RP disease;digenic mutations in the RDS and ROM1 Genes were also excluded.In summary,we couldn’t regard the D50H mutation in the RDS gene as the pathogenic factor of this ADRP family,which was the single nucleotide polymorphism of the RDS gene.更多还原