Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene
Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene
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DOI：
10.1177/112067210701700624
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发表时间：
2007-11-01
影响因子：
1.7
通讯作者：
Torricelli, F.
中科院分区：
文献类型：
--
作者：
Passerini, I.;Sodi, A.;Torricelli, F.
目的.描述一个意大利家族，其中两种不同的表型（视网膜色素变性和成人发病卵黄状黄斑营养不良）与外周蛋白/RDS基因中的相同突变（S212 G）相关。这种突变在视网膜色素变性患者中已有报道，但以前从未在成人发病卵黄状黄斑营养不良中检测到。一位38岁女性主诉双侧轻度视物变形，眼科检查显示成人型卵黄状黄斑营养不良的临床表型。她62岁的母亲临床诊断为视网膜色素变性，临床病程严重。结果。分子遗传学分析显示，两例患者RDS基因第2外显子的874 A → G突变导致S212 G的氨基酸改变。Peripherin/RDS S212 G突变可能对感光细胞盘结构的形成和稳定性具有破坏性影响，并且可能与不同的临床表型相关，即使在同一家族中也是如此。家族内表型变异已报告为其他RDS突变，这支持修饰基因或环境因素在RDS基因变异的临床表达的可能影响。此外，它表明，在视网膜变性和外周蛋白/RDS突变的患者中，应谨慎使用分子遗传学结果来预测疾病的临床过程和提供遗传咨询。
PURPOSE. To describe an Italian family in which two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. This mutation has already been reported in patients with retinitis pigmentosa, but it has never been previously detected in association with adult onset vitelliform macular dystrophy.METHODS. A 38-year-old woman complained of bilateral mild metamorphopsias and on ophthalmologic examination she showed the clinical phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother was clinically diagnosed with a retinitis pigmentosa, with a severe clinical course.RESULTS. In both patients, molecular genetic analysis revealed a 874A -> G transition in the exon 2 of the RDS gene leading to the amino acid change of S212G.CONCLUSIONS. Peripherin/RDS S212G mutation may have damaging effects on the formation and stability of the photoreceptors' disk structure and may be associated with different clinical phenotypes, even in the same family. Intrafamilial phenotypic variability has been reported for other RDS mutations; this supports the possible influence of modifier genes or environmental factors in the clinical expression of RDS gene variants. Moreover, it suggests that in patients with retinal degeneration and peripherin/RDS mutation, caution should be taken both in using molecular genetic results to predict the clinical course of the disease and in offering genetic counseling.