Autosomal-recessive early-onset retinitis pigmentosa caused by a mutation in PDE6G, the gene encoding the gamma subunit of rod cGMP phosphodiesterase

Liron Dvir, Gassoub Srour, Rasmi Abu-Ras, Benjamin Miller, Stavit A. Shalev, Tamar Ben-Yosef

Research output: Contribution to journalArticlepeer-review


Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4000. Over 30 genes and loci have been implicated in nonsyndromic autosomal-recessive (ar) RP. Genome-wide homozygosity mapping was conducted in two sibships from an extended consanguineous Muslim Arab Israeli family segregating ar severe early-onset RP. A shared homozygous region on chromosome 17q25.3 was identified in both sibships, with an overlap of 4.7 Mb. One of the genes located in this interval is PDE6G, encoding for the inhibitory γ subunit of rod photoreceptor cyclic GMP-phosphodiesterase. Mutations in the genes encoding for the catalytic subunits of this holoenzyme, PDE6A and PDE6B, cause arRP. Sequencing of all coding exons, including exon-intron boundaries, revealed a homozygous single base change (c.187+1G>T) located in the conserved intron 3 donor splice site of PDE6G. This mutation cosegregated with the disease in the extended family. We used an in vitro splicing assay to demonstrate that this mutation leads to incorrect splicing. Affected individuals had markedly constricted visual fields. Both scotopic and photopic electroretinograms were severely reduced or completely extinct. Funduscopy showed typical bone spicule-type pigment deposits spread mainly at the midperiphery, as well as pallor of the optic disk. Macular involvement was indicated by the lack of foveal reflex and typical cystoid macular edema, proved by optical coherence tomography. These findings demonstrate the positive role of the γ subunit in maintaining phosphodiesterase activity and confirm the contribution of PDE6G to the etiology of RP in humans.

Original languageEnglish
Pages (from-to)258-264
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - 13 Aug 2010
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to the patients and their relatives for their participation in this study. We thank Karl Skorecki and Dror Sharon for DNA samples and Liliana Mizrahi-Meissonnier for technical help. This work was supported by research grants from the Legacy Heritage Bio-Medical program of the Israel Science Foundation (to T.B.-Y.) and from the R.L. Kohns Eye Research Fund (to T.B.-Y. and S.A.S.).

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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