Mutation Spectrum of EYS in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa
Por:
Barragan, I, Borrego, S, Pieras, JI, Gonzalez-del Pozo, M, Santoyo, J, Ayuso, C, Baiget, M, Millan, JM, Mena, M, El-Aziz, MMA, Audo, I, Zeitz, C, Littink, KW, Dopazo, J, Bhattacharya, SS, Antinolo, G
Publicada:
1 nov 2010
Resumen:
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. (C) 2010 Wiley-Liss, Inc.
Filiaciones:
Barragan, I:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
Borrego, S:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
Pieras, JI:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
Gonzalez-del Pozo, M:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
Santoyo, J:
Ctr Invest Principe Felipe, Dept Bioinformat & Genom, Valencia, Spain
Ayuso, C:
Fdn Jimenez Diaz, Dept Genet, Inst Invest Sanitaria, E-28040 Madrid, Spain
Baiget, M:
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Millan, JM:
Hosp Univ La Fe, Unidad Genet, Valencia, Spain
Mena, M:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
El-Aziz, MMA:
UCL Inst Ophthalmol, London EC1V 9EL, England
Audo, I:
INSERM, U968, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Univ Paris 06, UMR S 968, Inst Vis, F-75012 Paris, France
Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, CIC 503, DHOS, F-75012 Paris, France
Inst Ophthalmol, Dept Mol Genet, London, England
Zeitz, C:
INSERM, U968, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Univ Paris 06, UMR S 968, Inst Vis, F-75012 Paris, France
Littink, KW:
Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6500 HB Nijmegen, Netherlands
Rotterdam Eye Hosp, NL-3000 LM Rotterdam, Netherlands
Bhattacharya, SS:
Andalusian Mol Biol & Regenerat Med Ctr CABIMER, Dept Cellular Therapy & Regenerat Med, Seville 1092, Spain
Antinolo, G:
Univ Seville, Unidad Gest Clin Genet Reprod & Med Fetal, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
Green Published
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