Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa.
Bottom Line: 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.
Affiliation: Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Sevilla, Spain.Show MeSH
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Mentions: In this study, 12 novel very likely pathogenic changes have been identified in 10 families. Of these 10 families, 5 present mutations in both alleles, whereas the remaining 5 have mutations in just one allele. The clearly pathogenic variants consisted of 6 truncating mutations, 1 in frame deletion of 300 nucleotides leading to a protein truncation of 100 aminoacids, 1 splice site mutation and 4 missense changes. Out of the 28 novel variations, we have also identified 5 possible pathogenic changes in 5 separate families. In addition, we have detected 3 pathogenic variations previously published in ours and other populations [Abd El-Aziz et al., 2008; Collin et al., 2008] (Table 2, Table 3, Figs. 3 and 4). As mentioned in the Methods section, the sequence variants were designated in accordance with the Human Genome Variation Society recommendations (http://www.hgvs.org/mutnomen/). All the patients with mutations had received a defined clinical diagnosis of RP with a recessive mode of inheritance and were Spanish. The variations were regarded as pathogenic changes as long as they met the criteria of pathogenicity, i.e absence in 200 control individuals and the segregation with the disease phenotype within the family (Fig. 4). Particularly, missense mutations were considered pathogenic according to their effect on functional EYS domains that they target, their evolutionary conservation and/or to the fact that they are found together with a second variant, especially if this is truncating.
Affiliation: Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Sevilla, Spain.