Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa

Isabel Barragan (1, 2) , Salud Borrego (1, 2) , Juan Ignacio Pieras (1, 2) , María González-del Pozo (1, 2) , Javier Santoyo (2, 3) , Carmen Ayuso (2, 4) , Montserrat Baiget (2, 5) , José María Millán (2, 6) , Marcela Daniela Mena (1, 2) , Mai Abd El-Aziz (7) , Isabelle Audo (8, 9, 10) , Christina Zeitz (8) , Karin W Littink (11, 12) , Joaquín Dopazo (2, 3) , Shomi Bhattacharya (13) , Guillermo Antiñolo (1, 2)

1 Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Instituto de Biomedicina de Sevilla (IBIS)
2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
3 Departamento de Bioinformática y Genómica
4 Departamento de Genética
5 Servei de Genética
6 Unidad de Genética
7 UCL-Institute of Ophthalmology
8 Institut de la Vision
9 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
10 Department of Molecular Genetics
11 Department of Human Genetics
12 The Rotterdam Eye Hospital
13 Celular Therapy and Regenerative Medicine

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.

Mots clés: Life Sciences

Isabel Barragan, Salud Borrego, Juan Ignacio Pieras, María González-del Pozo, Javier Santoyo, et al.. Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa. Human Mutation, 2010, 31 (11), ⟨10.1002/humu.21334⟩. ⟨hal-00573065⟩