A Novel Mutation and Phenotypes in Phosphodiesterase 6 Deficiency

Tsang, Stephen H.; Tsui, Irena; Chou, Chai Lin; Zernant, Jana; Haamer, Eneli; Iranmanesh, Reza; Tosi, Joaquin; Allikmets, Rando

doi:10.1016/j.ajo.2008.06.017

« Previous Next »American Journal of Ophthalmology
Volume 146, Issue 5 , Pages 780-788.e1, November 2008

A Novel Mutation and Phenotypes in Phosphodiesterase 6 Deficiency

Stephen H. Tsang
- Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, New York, New York
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York
- Inquiries to Stephen H. Tsang, 635 West 165th Street, Room 218, New York, NY 10032
Irena Tsui
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York
Chai Lin Chou
- Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, New York, New York
Jana Zernant
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York
Eneli Haamer
- Asper Ophthalmics, Tartu, Estonia
Reza Iranmanesh
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York
Joaquin Tosi
- Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, New York, New York
Rando Allikmets
- Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, New York, New York
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York

Accepted 13 June 2008. published online 26 August 2008.

Purpose

To develop a systematic approach for the molecular diagnosis of retinitis pigmentosa (RP) and to report new genotype-phenotype correlations for phosphodiesterase 6 (PDE6)-based RP mutations.

Design

Clinical and molecular studies on a retrospective case series.

Methods

We screened 40 unrelated RP patients with an autosomal recessive RP microarray. Individuals with RP caused by PDE6 deficiency underwent genetic segregation and phenotype analysis.

Results

A disease-associated allele was identified in 32% of patients. Two probands (5%) had PDE6 mutations. The first proband was a compound heterozygote for known R102C and N216S alleles in PDE6A (MIM#180071). Pedigree analysis determined that the N216S variant was benign and direct sequencing discovered a novel, S303C allele. The second proband had a homozygous D600N mutation in the PDE6B gene (MIM#180072). Visual acuities of PDE6-deficient patients ranged from 20/40 to 20/200. Clinical studies showed unusual vitreomacular traction, cystoid macular edema, macular atrophy, and ring hyperfluorescence in PDE6-deficient patients. Such extensive vitreoretinal degeneration is not characteristic of photoreceptor-specific enzyme deficiencies.

Conclusion

High-throughput deoxyribonucleic acid microarray chips can be used in combination with clinical imaging to precisely characterize patients with RP. Identifying the precise mutation in RP may become the standard of care as gene therapy emerges.