Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation

PLoS One. 2014 Jan 15;9(1):e85752. doi: 10.1371/journal.pone.0085752. eCollection 2014.

Abstract

X-linked Retinitis Pigmentosa (XLRP) accounts for 10-20% of all RP cases, and represents the most severe subtype of this disease. Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene are the most common causes of XLRP, accounting for over 70-75% of all XLRP cases. In this work, we analyzed all the exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of these with a provisional diagnosis of adRP but without male-to-male transmission. Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG) and two known nonsense mutations (c.851C→G and c.2260G→T) were identified in five families. Two novel deletions (c.2233_34delAG and c.2236_37delGA) resulted in the same frame shift (p.E746RfsX22), created similar phenotype in Family 3 and 4. The novel deletion (c.2403_04delAG; p.E802GfsX31) resulted in both XLRP and x-linked cone-rod dystrophy within the male patients of family 5, which suggested the presence of either genetic or environmental modifiers, or both, play a substantial role in disease expression. Genotype-phenotype correlation analysis suggested that (1) both patients and female carriers with mutation in Exon 8 (Family 1) manifest more severe disease than did those with ORF15 mutations (Family 2&3&4); (2) mutation close to downstream of ORF15 (Family 5) demonstrate the early preferential loss of cone function with moderate loss of rod function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Case-Control Studies
  • Child
  • China
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Female
  • Frameshift Mutation
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Pedigree
  • Retinitis Pigmentosa / genetics*
  • Sequence Deletion

Substances

  • Codon, Nonsense
  • Eye Proteins
  • RPGR protein, human

Grant support

This study was supported by the National Natural Science Foundation of China (http://www.nsfc.gov.cn/ Grant Number: 81170877 LY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.