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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. © 2010 Wiley-Liss, Inc.

Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60% of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40% of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001.