Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa.
Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa.
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发表时间：
1997-09
影响因子：
4.4
通讯作者：
T. Dryja;L. B. Hahn;K. Kajiwara;E. Berson
中科院分区：
文献类型：
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作者：
T. Dryja;L. B. Hahn;K. Kajiwara;E. Berson
目的测量视网膜色素变性（RP）病例中由外周蛋白/RDS（RDS）和ROM 1基因突变引起的比例。方法采用单链构象多态性（SSCP）分析方法，对227例显性或隐性RP患者和315例重叠的非亲缘关系患者（排除其他已知RP基因的患者）进行RDS基因突变分析。通过基于聚合酶链反应的直接基因组测序，并在可能的情况下，通过共分离分析的索引情况下的家庭中的变异带进行了进一步研究。结果发现四个索引患者有RP的结果之一，在RDS基因的四个显性突变，其中两个是新的。其他四个索引患者被发现有双基因RP作为RDS和ROM 1基因的杂合突变的组合的结果，其中一个ROM 1突变是新的。双基因病例都有相同的RDS突变（错义突变Leu 185 Pro），但每个病例都有三种不同的ROM 1突变之一。作者无法通过共分离分析确定RDS基因中的其他三个变化和ROM 1基因中的五个变化是否是致病性的。结论RDS基因突变是显性或双基因型RP的原因，而ROM 1基因突变是双基因型RP的原因。迄今为止，尚未发现单独由ROM 1突变引起的RP病例。RDS和ROM 1基因突变是RP的罕见原因，在美国和加拿大仅占患者的百分之几。
PURPOSE To measure the proportion of cases of retinitis pigmentosa (RP) caused by mutations in the peripherin/RDS (RDS) and ROM1 genes. METHODS The single-strand conformation polymorphism (SSCP) method was used to analyze 227 unrelated patients with dominant or recessive RP for mutations in the RDS gene and an overlapping set of 315 unrelated patients for mutations in the ROM1 gene (excluding patients with other known RP genes). Variant bands revealed by SSCP were studied further by polymerase chain reaction-based, direct genomic sequencing and, where possible, by cosegregation analysis in the families of the index cases. RESULTS Four index patients were found to have RP as a result of one of four dominant mutations in the RDS gene, two of which are novel. Four other index patients were found to have digenic RP as a result of the combination of heterozygous mutations in both the RDS and the ROM1 gene, with one of the ROM1 mutations being novel. The digenic cases all had the same RDS mutation (the missense change Leu185Pro), but each had one of three different ROM1 mutations. The authors were unable to determine through cosegregation analysis whether three other changes encountered in the RDS gene and five in the ROM1 gene were pathogenic. CONCLUSIONS The authors found mutations in the RDS gene as a cause of dominant or digenic RP and mutations in the ROM1 gene as a cause of digenic RP. No cases of RP caused by ROM1 mutations alone have been discovered thus far. Mutations in the RDS and ROM1 genes are infrequent causes of RP, together accounting for only a few percent of patients in the United States and Canada.