Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa.
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 space maker (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.
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.
Isabel
I
Barragán
Salud
S
Borrego
Juan Ignacio
JI
Pieras
María
M
González-del Pozo
Javier
J
Santoyo
Carmen
C
Ayuso
Montserrat
M
Baiget
José M
JM
Millan
Marcela
M
Mena
Mai M
MM
Abd El-Aziz
Isabelle
I
Audo
Christina
C
Zeitz
Karin W
KW
Littink
Joaquín
J
Dopazo
Shomi S
SS
Bhattacharya
Guillermo
G
Antiñolo
D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013030:Spain; D040681:Structural Homology, Protein
D029721:Drosophila Proteins; C533105:EYS protein, human; D005136:Eye Proteins; C514625:eys protein, Drosophila