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Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans
  1. M J Nevet1,
  2. S A Shalev2,
  3. J Zlotogora3,
  4. N Mazzawi4,
  5. T Ben-Yosef1
  1. 1Department of Genetics and The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  2. 2Genetics Institute, Ha'Emek Medical Center, Afula, Israel
  3. 3Department of Community Genetics, Public Health Services, Ministry of Health and the Hebrew University, Jerusalem, Israel
  4. 4Department of Ophthalmology, Ha'Emek Medical Center, Afula, Israel
  1. Correspondence to Dr Tamar Ben-Yosef, Department of Genetics, Rappaport Faculty of Medicine, Technion, PO Box 9649, Bat Galim, Haifa 31096, Israel; benyosef{at}tx.technion.ac.il

Abstract

Background Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. At least 32 genes and loci have been implicated in non-syndromic autosomal recessive RP. Progressive rod–cone degeneration is a canine form of autosomal recessive retinal degeneration, which serves as an animal model for human RP, and is caused by a missense mutation of the PRCD gene. The same homozygous PRCD mutation has been previously identified in a single human RP patient from Bangladesh. To date, this is the only RP-causing mutation of PRCD reported in humans.

Methods The cause of the high incidence rate of autosomal recessive RP in an isolated Muslim Arab village in Northern Israel was investigated by haplotype analysis in affected families. The underlying mutation was detected by direct sequencing of the causative gene, and its prevalence in affected and unaffected individuals from the village was determined. Patients who were homozygotes for this mutation underwent ophthalmic evaluation, including funduscopy and electroretinography.

Results and conclusions The identification of a novel pathogenic nonsense mutation of PRCD is reported. This founder mutation was found in a homozygous state in 18 patients from nine families, and its carrier frequency in the investigated village is 10%. The mutation is associated with a typical RP phenotype, including bone spicule-type pigment deposits and non-recordable electroretinograms. Additional findings include signs of macular degeneration and cataract. The identification of a second pathogenic mutation of PRCD in multiple RP patients confirms the role of PRCD in the aetiology of RP in humans.

  • Retina
  • retinitis pigmentosa
  • PRCD
  • founder mutation

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Footnotes

  • Funding The R.L. Kohns Eye Research Fund, Technion,Haifa, Israel. The Chief Scientist at the Israeli Ministry of Health, Jerusalem, Israel

  • Competing interests None

  • Patients consent Obtained.

  • Ethics approval This study was conducted with the approval of the National Helsinki Committee for Genetic Research in Humans, Israel

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