Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype.
OBJECTIVE
To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome.


METHODS
Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT).


RESULTS
The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change.


CONCLUSIONS
USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.
Schwartz
Sharon B
SB
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Aleman
Tomas S
TS
Cideciyan
Artur V
AV
Windsor
Elizabeth A M
EA
Sumaroka
Alexander
A
Roman
Alejandro J
AJ
Rane
Tej
T
Smilko
Elaine E
EE
Bennett
Jean
J
Stone
Edwin M
EM
Kimberling
William J
WJ
Liu
Xue-Zhong
XZ
Jacobson
Samuel G
SG
D000293:Adolescent; D000328:Adult; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D035781:Siblings; D013577:Syndrome; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields
C417525:ADGRV1 protein, human; D016326:Extracellular Matrix Proteins; D043562:Receptors, G-Protein-Coupled; C112735:USH2A protein, human