A novel mutation and phenotypes in phosphodiesterase 6 deficiency.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Tsang
Stephen H
SH
Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, New York, New York, USA. sht2@columbia.edu
Tsui
Irena
I
Chou
Chai Lin
CL
Zernant
Jana
J
Haamer
Eneli
E
Iranmanesh
Reza
R
Tosi
Joaquin
J
Allikmets
Rando
R
D000328:Adult; D000369:Aged, 80 and over; D000483:Alleles; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000172:deficiency* / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D012189:Retrospective Studies; D014792:Visual Acuity
D005136:Eye Proteins; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C410522:PDE6A protein, human; C517431:PDE6B protein, human