title: Spectrum of SPATA7 mutations in Leber congenital amaurosis and delineation of the associated phenotype.
abstract: Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration. It may present as a congenital stationary cone-rod dystrophy (LCA type I) or a progressive yet severe rod-cone dystrophy (LCA type II). Twelve LCA genes have been identified, three of which account for Type I and nine for LCA type II. All proteins encoded by these genes but two are preferentially expressed in the retina and are responsible for non-syndromic LCA only. By contrast LCA5 and CEP290 are widely expressed and mutations in this latter result in a variety of phenotypes from non-syndromic retinal degeneration to pleiotropic disorders including senior-Loken (SNLS) and Joubert syndromes (JBTS). Recently, mutations in the widely expressed gene SPATA7 were reported to cause LCA or juvenile retinitis pigmentosa. The purpose of this study was i) to determine the level of expression of two major alternative SPATA7 transcripts in a large range of tissues and ii) to assess the involvement of this novel gene in a large cohort of unrelated patients affected with LCA (n = 134). Here, we report high SPATA7expression levels in retina, brain and testis with differential expression of the two transcripts. SPATA7 mutations were identified in few families segregating non-syndromic LCA (n = 4/134). Six different mutations were identified, four of which are novel; All affected both SPATA7 transcripts. The clinical evaluation of patients suggested that SPATA7 mutations account for the rod-cone dystrophy type of the disease.
authors.affiliation: Unité de Recherches Génétique et Epigénétique des Maladies Métaboliques, Neurosensorielles et du Développement, INSERM U781 and Université Paris Descartes, CHU Necker Enfants Malades, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perrault
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hanein
authors.forename: Xavier
authors.initials: X
authors.lastname: Gerard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delphin
authors.forename: Lucas
authors.initials: L
authors.lastname: Fares-Taie
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gerber
authors.forename: Valérie
authors.initials: V
authors.lastname: Pelletier
authors.forename: Emilie
authors.initials: E
authors.lastname: Mercé
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Bernard
authors.initials: B
authors.lastname: Puech
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort-Dhellemmes
authors.forename: Michael D
authors.initials: MD
authors.lastname: Petersen
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zafeiriou
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Olivier
authors.initials: O
authors.lastname: Roche
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; C482323:SPATA7 protein, human