RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa.
OBJECTIVE
To assess the phenotype of patients with X-linked retinitis pigmentosa (XLRP) with RP2 mutations and to correlate the findings with their genotype.


METHODS
Six hundred eleven patients with RP were screened for RP2 mutations. From this screen, 18 patients with RP2 mutations were evaluated clinically with standardized electroretinography, Goldmann visual fields, and ocular examinations. In addition, 7 well-documented cases from the literature were used to augment genotype-phenotype correlations.


RESULTS
Of 11 boys younger than 12 years, 10 (91%) had macular involvement and 9 (82%) had best-corrected visual acuity worse than 20/50. Two boys from different families (aged 8 and 12 years) displayed a choroideremia-like fundus, and 9 boys (82%) were myopic (mean error, -7.97 diopters [D]). Of 10 patients with electroretinography data, 9 demonstrated severe rod-cone dysfunction. All 3 female carriers had macular atrophy in 1 or both eyes and were myopic (mean, -6.23 D). All 9 nonsense and frameshift and 5 of 7 missense mutations (71%) resulted in severe clinical presentations.


CONCLUSIONS
Screening of the RP2 gene should be prioritized in patients younger than 16 years characterized by X-linked inheritance, decreased best-corrected visual acuity (eg, >20/40), high myopia, and early-onset macular atrophy. Patients exhibiting a choroideremia-like fundus without choroideremia gene mutations should also be screened for RP2 mutations.


CONCLUSIONS
An identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.
Jayasundera
Thiran
T
Department of Ophthalmologyand Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Branham
Kari E H
KE
Othman
Mohammad
M
Rhoades
William R
WR
Karoukis
Athanasios J
AJ
Khanna
Hemant
H
Swaroop
Anand
A
Heckenlively
John R
JR
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology
D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; D019204:GTP-Binding Proteins