Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains

Hum Mutat. 2001 Aug;18(2):109-19. doi: 10.1002/humu.1160.


X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes. In the attempt to assess the degree of involvement of the RP2 gene, we performed a complete mutation analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mutations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect. Our mutation analysis confirms the percentage of RP2 mutations detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cohort Studies
  • Conserved Sequence / genetics
  • DNA Mutational Analysis
  • Ethnicity / genetics
  • Exons / genetics
  • Female
  • Genetic Heterogeneity
  • Genetic Linkage / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Tertiary
  • Retinitis Pigmentosa / genetics*
  • Sequence Alignment
  • Sequence Homology
  • X Chromosome / genetics*