Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population

PLoS One. 2012;7(7):e41902. doi: 10.1371/journal.pone.0041902. Epub 2012 Jul 27.


Background: Retinitis pigmentosa and other hereditary retinal degenerations (HRD) are rare genetic diseases leading to progressive blindness. Recessive HRD are caused by mutations in more than 100 different genes. Laws of population genetics predict that, on a purely theoretical ground, such a high number of genes should translate into an extremely elevated frequency of unaffected carriers of mutations. In this study we estimate the proportion of these individuals within the general population, via the analyses of data from whole-genome sequencing.

Methodology/principal findings: We screened complete and high-quality genome sequences from 46 control individuals from various world populations for HRD mutations, using bioinformatic tools developed in-house. All mutations detected in silico were validated by Sanger sequencing. We identified clear-cut, null recessive HRD mutations in 10 out of the 46 unaffected individuals analyzed (∼22%).

Conclusions/significance: Based on our data, approximately one in 4-5 individuals from the general population may be a carrier of null mutations that are responsible for HRD. This would be the highest mutation carrier frequency so far measured for a class of Mendelian disorders, especially considering that missenses and other forms of pathogenic changes were not included in our assessment. Among other things, our results indicate that the risk for a consanguineous couple of generating a child with a blinding disease is particularly high, compared to other genetic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genomics
  • Humans
  • Internationality
  • Mutation Rate*
  • Retinitis Pigmentosa / genetics*

Grant support

This work was supported by the Swiss National Science Foundation (Grant Number 310030_138346) and the Gebert Rüf Foundation (Rare Diseases - New Technologies grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.