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J. Kaplan, I. Perrault, S. Hanein, S. Gerber, J.–L.L. Dufier, A. Munnich, J.–M.M. Rozet; A Novel Mutation in the GUCY2D Gene Responsible for an Early–Onset Severe RP Different From the Usual GUCY2D–LCA Phenotype . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1810.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To understand the recurrence of LCA in a child born to two patients affected with different retinal disorders: a typical GUCY2D–LCA phenotype for the mother and an early–onset severe retinitis pigmentosa (RP) for the father. Methods:The 18 coding exons of GUCY2D were screened for mutations by Denaturing High Pressure Liquid Chromatography (DHPLC) and direct sequencing using specific primers in the three affected individuals of this family. Results: The screening of the GUCY2D gene in the family revealed that the mother was compound heterozygous for two mutations: c.3043+4A>T and c.2943delG while the father carried a homozygous 4bp insertion in exon 19 (c.3236insACCA) leading to a 28 amino acids elongation of the protein. The affected infant was compound heterozygous for the paternal insertion and the maternal c.3043+4A>T mutation. Conclusions: 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 occurrence of an early–onset severe RP, different from LCA, resulting from homozygosity for a 4 bp insertion in GUCY2D. Interestingly, this 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.
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