Passerini I, Sodi A, Giambene B, Menchini U, Torricelli F
Department of Genetic Diagnosis, Careggi University Hospital, Firenze, Italy.
Eur J Ophthalmol. 2007 Nov-Dec;17(6):1000-3. doi: 10.1177/112067210701700624.
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.
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.
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.
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.
描述一个意大利家庭，其中两种不同的表型（视网膜色素变性和成人型卵黄样黄斑营养不良）与外周蛋白/RDS基因中的同一突变（S212G）相关。该突变已在视网膜色素变性患者中报道过，但此前从未在与成人型卵黄样黄斑营养不良相关的病例中检测到。
一名38岁女性主诉双眼轻度视物变形，眼科检查显示其具有成人型卵黄样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，病情严重。
在两名患者中，分子遗传学分析均显示RDS基因外显子2中存在874A→G转换，导致氨基酸由S212变为G。
外周蛋白/RDS的S212G突变可能对视锥细胞盘状结构的形成和稳定性产生破坏作用，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。其他RDS突变也有家族内表型变异性的报道；这支持修饰基因或环境因素可能对RDS基因变异的临床表达产生影响。此外，这表明对于患有视网膜变性且存在外周蛋白/RDS突变的患者，在利用分子遗传学结果预测疾病临床进程以及提供遗传咨询时都应谨慎。
