Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype.
OBJECTIVE
To determine the prevalence of mutations in the EYS gene in a cohort of patients affected by autosomal recessive retinitis pigmentosa (RP) and to describe the associated phenotype.


METHODS
Case series.


METHODS
Two hundred forty-five patients affected by autosomal recessive RP.


METHODS
All coding exons of EYS were screened for mutations by polymerase chain reaction amplification and sequence analysis. All 12 patients carrying mutations in EYS were re-examined, which included Goldmann kinetic perimetry, electroretinography, and high-resolution spectral-domain optical coherence tomography (OCT).


METHODS
DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field assessments using Goldmann kinetic perimetry, electroretinogram responses, and OCT images.


RESULTS
Nine novel truncating mutations and one previously described mutation in EYS were identified in 11 families. In addition, 18 missense changes of uncertain pathogenicity were found. Patients carrying mutations in EYS demonstrated classic RP with night blindness as the initial symptom, followed by gradual constriction of the visual field and a decline of visual acuity later in life. The onset of symptoms typically occurred between the second and fourth decade of life. The fundus displayed bone spicules increasing in density with age and generalized atrophy of the retinal pigment epithelium and choriocapillaris with relative sparing of the posterior pole until later in the disease process, when atrophic macular changes occurred.


CONCLUSIONS
Mutations in EYS account for approximately 5% of autosomal recessive RP patients in a cohort of patients consisting predominantly of patients of western European ancestry. The EYS-associated RP phenotype is typical and fairly homogeneous in most patients.
The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
Karin W
KW
Littink
L Ingeborgh
LI
van den Born
Robert K
RK
Koenekoop
Rob W J
RW
Collin
Marijke N
MN
Zonneveld
Ellen A W
EA
Blokland
Hayat
H
Khan
Thomas
T
Theelen
Carel B
CB
Hoyng
Frans P M
FP
Cremers
Anneke I
AI
den Hollander
B Jeroen
BJ
Klevering
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012160:Retina / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests
C533105:EYS protein, human; D005136:Eye Proteins