TY - JOUR
T1 - A novel RDS/peripherin gene mutation associated with diverse macular phenotypes
AU - Yang, Zhenglin
AU - Li, Yang
AU - Jiang, Li
AU - Karan, Goutam
AU - Moshfeghi, Darius M.
AU - O'Connor, Scott T.
AU - Li, Xi
AU - Yu, Zhengya
AU - Lewis, Hilel
AU - Zack, Donald J.
AU - Jacobson, Samuel G.
AU - Zhang, Kang
N1 - Funding Information:
We thank Dr. Andrew Goldberg for his helpful comments and critical review of the manuscript. This work is supported by American Health Assistance Foundation, The Helen Keller Eye Research Foundation, Fight For Sight, The Knights Templar Eye Research Foundation, The Ruth and Milton Steinbach Fund, Foundation Fighting Blindness, Macula Vision Research Foundation, Ronald McDonald House Charities, Macular Disease Foundation, NIH EY013868, EY05627, EY14428, EY14448, and Grant Ritter Fund. SGJ is a Research to Prevent Blindness Senior Scientific Investigator. DJZ is the Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology.
PY - 2004/6
Y1 - 2004/6
N2 - Pattern dystrophy is a heterogeneous group of retinal dystrophies of which butterfly-shaped pattern dystrophy (BPD) and adult-onset foveomacular dystrophy (AOFMD) are the two most common forms. BPD is characterized by a butterfly-shaped, irregular, depigmented lesion at the level of the retinal pigment epithelium. In contrast, AOFMD is characterized by the presence of slightly elevated, symmetric, solitary, round to oval, yellow lesions at the level of the retinal pigment epithelium. We identified three independent kindreds with pattern dystrophy, one with four patients affected with BPD and the other two with 14 affected patients with AOFMD. We performed complete ophthalmic examination, fluorescein angiography, linkage mapping, and mutational screening in the RDS/peripherin gene in the affected patients. Patients affected with BPD had a best-corrected vision of 20/20 to 20/25, whereas vision in the eyes of patients with AOFMD ranged from 20/20 to 20/400. In all three kindreds, sequence analysis identified an A-to-G change at nucleotide position 422 of the RDS/peripherin gene, predicting a novel Tyr-141-CYs substitution. A haplotype analysis revealed that these three kindreds shared an identical disease haplotype at the RDS/peripherin locus, indicating that the mutation reflects a founder effect. The sequence change that segregated with the disease phenotype was not observed in 200 control chromosomes. Our results identified a novel mutation in the RDS/peripherin gene that can cause diverse macular phenotypes. Genetic and clinical investigation of pattern dystrophy may provide useful diagnostic tools and new treatment strategies for this disorder.
AB - Pattern dystrophy is a heterogeneous group of retinal dystrophies of which butterfly-shaped pattern dystrophy (BPD) and adult-onset foveomacular dystrophy (AOFMD) are the two most common forms. BPD is characterized by a butterfly-shaped, irregular, depigmented lesion at the level of the retinal pigment epithelium. In contrast, AOFMD is characterized by the presence of slightly elevated, symmetric, solitary, round to oval, yellow lesions at the level of the retinal pigment epithelium. We identified three independent kindreds with pattern dystrophy, one with four patients affected with BPD and the other two with 14 affected patients with AOFMD. We performed complete ophthalmic examination, fluorescein angiography, linkage mapping, and mutational screening in the RDS/peripherin gene in the affected patients. Patients affected with BPD had a best-corrected vision of 20/20 to 20/25, whereas vision in the eyes of patients with AOFMD ranged from 20/20 to 20/400. In all three kindreds, sequence analysis identified an A-to-G change at nucleotide position 422 of the RDS/peripherin gene, predicting a novel Tyr-141-CYs substitution. A haplotype analysis revealed that these three kindreds shared an identical disease haplotype at the RDS/peripherin locus, indicating that the mutation reflects a founder effect. The sequence change that segregated with the disease phenotype was not observed in 200 control chromosomes. Our results identified a novel mutation in the RDS/peripherin gene that can cause diverse macular phenotypes. Genetic and clinical investigation of pattern dystrophy may provide useful diagnostic tools and new treatment strategies for this disorder.
KW - Adult-onset foveomacular dystrophy
KW - Butterfly-shaped pattern dystrophy
KW - RDS/peripherin gene
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U2 - 10.1080/13816810490514388
DO - 10.1080/13816810490514388
M3 - Article
C2 - 15370544
AN - SCOPUS:6344254498
SN - 1381-6810
VL - 25
SP - 133
EP - 145
JO - Ophthalmic genetics
JF - Ophthalmic genetics
IS - 2
ER -