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I. Perrault, S. Hanein, X. Gerard, N. Delphin, H. Dollfus, S. Defoort-Dhellemmes, J. Kaplan, O. Roche, J.-M. Rozet; Spectrum of SPATA7 Mutations in Leber Congenital Amaurosis and Delineation of the Associated Phenotype. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3082.
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© ARVO (1962-2015); The Authors (2016-present)
Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration. Until recently, 12 genes involved in different physiological pathways of the photoreceptors or the RPE function were identified. Recently, mutations in the ubiquitously expressed gene SPATA7 were reported to cause LCA or juvenile retinitis pigmentosa. The purpose of this study was to determine the level of expression of SPATA7 in a large range of tissues and to assess its the involvement in a large cohort of patients affected with LCA.
The expression of the two major SPATA7 transcripts resulting from alternative splicing of exon 3, was examined by Real-time RT-PCR in adult and foetal human tissues using primers specific to each variant. On the other hand, genomic DNA of 134 patients affected with non-sydromic LCA and 2 patients presenting with JBTS, all of whom excluded know LCA or JBTS genes, were screened for SPATA7 mutations by direct sequencing using specific primers.
Highest expression levels of both major SPATA7 transcripts were found in sensorineural retina, cerebellum, whole brain and testis. The transcript variant containing exon 3 was more expressed than its counterpart in neuronal tissues whereas testis expressed higher levels of the transcript variant missing exon 3. The screening of the SPATA7 gene resulted in the identification of 7 disease alleles in 4/134 non-syndromic LCA families (4/4 of European ancestry, 1 familial and 4 sporadic cases, respectively). Six different mutations (1 homozygote) were found, four of which were novel and two were reported previously. Five out of six mutations were expected to truncate the protein and one affected the ATG initiation codon. All mutations were expected to alter both SPATA7 transcript variants. The age, mode of onset and phenotype were similar in the 4 families (5 affected patients) and fitted the exact definition of LCA type II i.e. an early and severe rod-cone dystrophy.
The contribution of SPATA7 in our series of families can be regarded as modest in LCA worldwide (1.7% of families with mutations - 1.1% of all LCA cases). This result contradicts the assumption reported earlier of an important role of this gene in the disease.
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