Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene.
OBJECTIVE
To estimate the mean rates of ocular function loss in patients with autosomal recessive retinitis pigmentosa due to USH2A mutations.


METHODS
In 125 patients with USH2A mutations, longitudinal regression was used to estimate mean rates of change in Snellen visual acuity, Goldmann visual field area (V4e white test light), and 30-Hz (cone) full-field electroretinogram amplitude. These rates were compared with those of previously studied cohorts with dominant retinitis pigmentosa due to RHO mutations and with X-linked retinitis pigmentosa due to RPGR mutations. Rates of change in patients with the Cys759Phe mutation, the USH2A mutation associated with nonsyndromic disease, were compared with rates of change in patients with the Glu767fs mutation, the most common USH2A mutation associated with Usher syndrome type II (i.e., retinitis pigmentosa and hearing loss).


RESULTS
Mean annual exponential rates of decline for the USH2A patients were 2.6% for visual acuity, 7.0% for visual field area, and 13.2% for electroretinogram amplitude. The rate of acuity loss fell between the corresponding rates for the RHO and RPGR patients, whereas the rates for field and ERG amplitude loss were faster than those for the RHO and RPGR patients. No significant differences were found for patients with the Cys759Phe mutation versus patients with the Glu767fs mutation.


CONCLUSIONS
On average, USH2A patients lose visual acuity faster than RHO patients and slower than RPGR patients. USH2A patients lose visual field and cone electroretinogram amplitude faster than patients with RHO or RPGR mutations. Patients with a nonsyndromic USH2A mutation have the same retinal disease course as patients with syndromic USH2A disease.
Sandberg
Michael A
MA
The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. masandberg@aol.com
Rosner
Bernard
B
Weigel-DiFranco
Carol
C
McGee
Terri L
TL
Dryja
Thaddeus P
TP
Berson
Eliot L
EL
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001766:Blindness / Q000503:physiopathology; D002648:Child; D018450:Disease Progression; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005500:Follow-Up Studies; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; C099929:RPGR protein, human; C112735:USH2A protein, human; D012243:Rhodopsin