title: A novel mutation in the GUCY2D gene responsible for an early onset severe RP different from the usual GUCY2D-LCA phenotype.
abstract: 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.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, Hôpital Necker - Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perrault
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hanein
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gerber
authors.forename: Beatrice
authors.initials: B
authors.lastname: Lebail
authors.forename: Patrice
authors.initials: P
authors.lastname: Vlajnik
authors.forename: Fabienne
authors.initials: F
authors.lastname: Barbet
authors.forename: Dominique
authors.initials: D
authors.lastname: Ducroq
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dufier
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
mesh_terms: D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase