Spectrum of SPATA7 mutations in Leber congenital amaurosis and delineation of the associated phenotype.
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.
Perrault
Isabelle
I
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.
Hanein
Sylvain
S
Gerard
Xavier
X
Delphin
Nathalie
N
Fares-Taie
Lucas
L
Gerber
Sylvie
S
Pelletier
Valérie
V
Mercé
Emilie
E
Dollfus
Hélène
H
Puech
Bernard
B
Defoort-Dhellemmes
Sabine
S
Petersen
Michael D
MD
Zafeiriou
Dimitrios
D
Munnich
Arnold
A
Kaplan
Josseline
J
Roche
Olivier
O
Rozet
Jean-Michel
JM
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
D004268:DNA-Binding Proteins; C482323:SPATA7 protein, human