A novel mutation in the GUCY2D gene responsible for an early onset severe RP different from the usual GUCY2D‐LCA phenotype
A novel mutation in the GUCY2D gene responsible for an early onset severe RP different from the usual GUCY2D‐LCA phenotype
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GUCY2D 基因中的一种新突变导致早发严重 RP 与通常的 GUCY2D-LCA 表型不同
作者：
I. Perrault;S. Hanein;S. Gerber;B. Lebail;Patrice Vlajnik;F. Barbet;D. Ducroq;J. Dufier;A. Munnich;J. Kaplan;J. Rozet
据报道，携带视网膜鸟苷酸环化酶（GUCY2D）基因突变的患者经常受到一种特殊形式的莱伯先天性黑内障（LCA）的影响，这种病被定义为“先天性静止锥杆营养不良伴高度远视、全视网膜变性和高度视力下降”。我们在此报告了两例不同视网膜疾病患者的研究：典型的GUCY2D - LCA表型和早发性严重视网膜色素变性（RP）。没想到，他们生下了一个患有LCA的婴儿。该家族的遗传研究表明，GUCY2D - LCA疾病是由两个严重GUCY2D突变（c.3043+4A>T, c.2943delG）的复合杂合性引起的，而早期发病的严重RP是由同一基因中4 bp插入的纯合性引起的，尽管表型差异明显（c.3236insACCA）。有趣的是，这个最后的突变除了会导致蛋白质的28个氨基酸延伸，这与所有GUCY2D突变相反，这些突变导致LCA被认为是空等位基因。该报告支持异常GUCY2D突变的存在，与典型的GUCY2D先天性静止锥杆营养不良相比，GUCY2D突变具有更温和和不同的表型。©2005 Wiley‐Liss, Inc。
Patients carrying mutations in the retinal guanylate cyclase (GUCY2D) gene were reported to be constantly affected with a particular form of Leber congenital amaurosis (LCA) defined as a “congenital stationary cone‐rod dystrophy with high hypermetropia, panretinal degeneration and highly reduced visual acuity”. We report here, the study of two patients affected with different retinal disorder: a typical GUCY2D‐LCA phenotype and early‐onset severe retinitis pigmentosa (RP). Unexpectedly, they gave birth to an infant suffering from LCA. The genetic study in the family allowed to explain the disease in the infant by showing that the GUCY2D‐LCA disease was accounted for by compound heterozygosity for two severe GUCY2D mutations (c.3043+4A>T, c.2943delG) while the early‐onset severe RP resulted from homozygosity for a 4 bp insertion in the same gene, despite the sound phenotypic differences (c.3236insACCA). Interestingly, this last mutation is excepted to result in a 28 amino acid elongation of the protein contrary to all GUCY2D mutations accounting for LCA which are expected to be null alleles. This report gives support to the existence of exceptional GUCY2D mutations accounting for a milder and different phenotype compared to the typical GUCY2D congenital stationary cone‐rod dystrophy. © 2005 Wiley‐Liss, Inc.