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Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa
Author(s) -
Barragán Isabel,
Borrego Salud,
Pieras Juan Ignacio,
Pozo María Gonzálezdel,
Santoyo Javier,
Ayuso Carmen,
Baiget Montserrat,
Millan José M.,
Mena Marcela,
ElAziz Mai M. Abd,
Audo Isabelle,
Zeitz Christina,
Littink Karin W.,
Dopazo Joaquín,
Bhattacharya Shomi S.,
Antiñolo Guillermo
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21334
Subject(s) - retinitis pigmentosa , genetics , single nucleotide polymorphism , gene , biology , mutation , population , medicine , genotype , environmental health
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding an ortholog of Drosophila spacemaker (spam) as a commonly mutated gene in autosomal recessive RP. In the present study, we report the identification of 73 sequence variations in EYS, of which 28 are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28) are possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have detected 3 pathogenic changes previously reported in other populations. We are also presenting the characterisation of EYS homologues in different species, and a detailed analysis of the EYS domains, with the identification of an interesting novel feature: a putative coiled‐coil domain. Majority of the mutations in the arRP patients have been found within the domain structures of EYS. The minimum observed prevalence of distinct EYS mutations in our group of patients is of 15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP in the Spanish population. Along with the detection of three recurrent mutations in Caucasian population, our hypothesis of EYS being the first prevalent gene in arRP has been reinforced in the present study. © 2010 Wiley‐Liss, Inc.