Genetic analysis of the rhodopsin gene identifies a mosaic dominant retinitis pigmentosa mutation in a healthy individual

Avigail Beryozkin, Gal Levy, Anat Blumenfeld, Segev Meyer, Prasanthi Namburi, Yair Morad, Libe Gradstein, Anand Swaroop, Eyal Banin, Dror Sharon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

PURPOSE. Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous hereditary retinal diseases that result in blindness due to photoreceptor degeneration. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP) and are responsible for 16% to 35% of adRP cases in the Western population. Our purpose was to investigate the contribution of RHO to adRP in the Israeli and Palestinian populations. METHODS. Thirty-two adRP families participated in the study. Mutation detection was performed by whole exome sequencing (WES) and Sanger sequencing of RHO exons. Fluorescence PCR reactions of serially diluted samples were used to predict the percentage of mosaic cells in blood samples. RESULTS. Eight RHO disease-causing mutations were identified in nine families, with only one novel mutation, c.548-638dup91bp, identified in a family where WES failed to detect any causal variant. Segregation analysis revealed that the origin of the mutation is in a mosaic healthy individual carrying the mutation in approximately 13% of blood cells. CONCLUSIONS. This is the first report of the mutation spectrum of a known adRP gene in the Israeli and Palestinian populations, leading to the identification of seven previously reported mutations and one novel mutation. Our study shows that RHO mutations are a major cause of adRP in this cohort and are responsible for 28% of adRP families. The novel mutation exhibits a unique phenomenon in which an unaffected individual is mosaic for an adRP-causing mutation.

Original languageEnglish
Pages (from-to)940-947
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number3
DOIs
StatePublished - 1 Mar 2016
Externally publishedYes

Keywords

  • Genetic defects
  • Inherited blindness
  • Mosaicism
  • Retinal degeneration
  • Rhodopsin

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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