RDS/peripherin gene mutations are frequent causes of central retinal dystrophies
RDS/peripherin gene mutations are frequent causes of central retinal dystrophies
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DOI：
10.1136/jmg.34.8.620
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发表时间：
1997-08-01
影响因子：
4
通讯作者：
Wissinger, B
中科院分区：
文献类型：
--
作者：
Kohl, S;ChristAdler, M;Wissinger, B
采用SSCP分析和直接DNA测序的方法，对76例不同形式的以中央视网膜营养不良为主的独立家族患者进行RDS/peripherin基因突变筛查。检测到2个无义突变（Gln239ter、Tyr285ter）， 5个错义突变（Arg172Trp、Lys197Glu、Gly208Asp、Trp246Arg、Ser289Leu）和1个单碱基插入（Gly208insG），所有病例均为杂合。这些突变中只有Arg172Trp是先前报道过的。可以在选定的家族中建立突变与疾病表型的共分离。其他错义突变从55-75名对照受试者中排除。患者的表型和疾病表达不仅在突变病例之间，而且在同一家族的受影响成员之间也表现出显著的差异。这项研究表明，RDS/外周蛋白突变是各种类型的中央视网膜营养不良的常见原因，RDS/外周蛋白基因表现出广泛的等位基因突变。对已知突变的比较分析使我们能够假设RDS/外周蛋白基因突变的有害作用是不同分子机制的结果。
Patients from 76 independent families with various forms of mostly central retinal dystrophies were screened for mutations in the RDS/peripherin gene by means of SSCP analysis and direct DNA sequencing. Two nonsense mutations (Gln239ter, Tyr285ter), five missense mutations (Arg172Trp, Lys197Glu, Gly208Asp, Trp246Arg, Ser289Leu), and one single base insertion (Gly208insG), heterozygous in all cases, were detected. Only one of these mutations, Arg172Trp, has been reported previously. Cosegregation of the mutation with the disease phenotype could be established in selected families. Other missense mutations were excluded from a panel of 55-75 control subjects. The patients showed remarkable variation in phenotype and disease expression not only between cases with mutations but also between affected members of the same family. This study indicates that RDS/peripherin mutations are a frequent cause of various types of central retinal dystrophies and that the RDS/peripherin gene exhibits a broad spectrum of allelic mutations. Comparative analysis of known mutations allowed us to hypothesise that the deleterious effect of RDS/peripherin gene mutations is the result of different molecular mechanisms.