Identification of novel mutations in the ortholog of Drosophila eyes shut gene (EYS) causing autosomal recessive retinitis pigmentosa.
OBJECTIVE
Recently, a novel gene was cloned for autosomal recessive retinitis pigmentosa (arRP), EYS, on 6q12. This study was conducted to determine the spectrum and frequency of EYS mutations in 195 unrelated patients with autosomal recessive and autosomal dominant RP (adRP).


METHODS
All cases had a complete ophthalmic examination, and the clinical diagnosis of RP was based on visual acuity, fundus photography, and electroretinography findings. The DNA extracted from all participants was subjected to molecular genetic analysis entailing amplification of the coding regions and exon-intron boundaries of EYS by polymerase chain reaction, followed by direct sequencing. Bioinformatics analysis was undertaken to study the effect of the identified mutations on protein structure and function.


RESULTS
Eleven novel missense, nonsense, and splice site mutations were identified within EYS in 10 unrelated arRP patients, with probable allele frequency of 11%. However, no mutations were observed in the adRP panel. In addition, 53 single-nucleotide polymorphisms (SNPs) were found, of which 12 were previously unreported. Bioinformatics analyses revealed that all mutations were highly conserved across other species and/or involved important domains on protein structure. Intrafamilial phenotypic variability was also observed in a family with double heterozygous mutations.


CONCLUSIONS
This is the first report of molecular genetic analysis of EYS in a cohort of unrelated British and Chinese patients with RP. The results further the initial hypothesis that EYS is a major causative gene for recessive RP and emphasize the role of different types of mutations in disrupting the function of EYS.
Abd El-Aziz
Mai M
MM
Department of Genetics, Institute of Ophthalmology, London, UK. m.saad@ucl.ac.uk
O'Driscoll
Ciara A
CA
Kaye
Rebecca S
RS
Barragan
Isabel
I
El-Ashry
Mohamed F
MF
Borrego
Salud
S
Antiñolo
Guillermo
G
Pang
Chi Pui
CP
Webster
Andrew R
AR
Bhattacharya
Shomi S
SS
D000328:Adult; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
C533105:EYS protein, human; D005136:Eye Proteins