Valverde Diana, Pereiro Ines, Vallespín Elena, Ayuso Carmen, Borrego Salud, Baiget Montserrat
Departamento de Bioquímica, Genética e Inmunología, Universidad de Vigo, Vigo, Spain.
Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1065-8. doi: 10.1167/iovs.08-2083. Epub 2008 Nov 14.
Several mutations have been described in the RDH12 gene that disturb the activity of the encoded protein, suggesting that RDH12 loss of function disrupts the synthetic pathway of the visual chromophore 11-cis-retinal, therefore resulting in early and progressive retinal degeneration (RD). Mutations in this gene have been related to autosomal recessive Leber congenital amaurosis (LCA) and to a form of autosomal recessive childhood-onset severe retinal dystrophy (CSRD). This study was undertaken to attempt to correlate the genotype and phenotype in Spanish CSRD and LCA patients who harbor RDH12 mutations.
A complete ophthalmic and electrophysiologic examination was performed according to preexisting protocols. A screening for mutations was then performed using denaturing HPLC on a DNA fragment analysis system. Those fragments bearing an abnormal pattern were sequenced.
Ten families bearing RDH12 mutations in homozygous or compound heterozygous form were found. All of them corresponded to patients with severe and early-onset retinal dystrophy.
The RDH12-associated phenotype is not homogeneous, the position and nature of the mutations clearly influence the pathologic expression of this disease.
已在RDH12基因中发现了几种突变，这些突变会干扰所编码蛋白质的活性，这表明RDH12功能丧失会破坏视觉发色团11-顺式视黄醛的合成途径，从而导致早期进行性视网膜变性（RD）。该基因的突变与常染色体隐性遗传性莱伯先天性黑蒙（LCA）以及常染色体隐性遗传性儿童期严重视网膜营养不良（CSRD）的一种形式有关。本研究旨在尝试将携带RDH12突变的西班牙CSRD和LCA患者的基因型与表型进行关联。
根据现有方案进行全面的眼科和电生理检查。然后在DNA片段分析系统上使用变性高效液相色谱法进行突变筛查。对那些具有异常模式的片段进行测序。
发现了10个以纯合或复合杂合形式携带RDH12突变的家族。所有这些家族的患者均患有严重的早发性视网膜营养不良。
RDH12相关的表型并不一致，突变的位置和性质明显影响该疾病的病理表现。
