X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15

Am J Hum Genet. 2002 Apr;70(4):1049-53. doi: 10.1086/339620. Epub 2002 Feb 20.


X-linked cone-rod dystrophy (COD1) is a retinal disease that primarily affects the cone photoreceptors; the disease was originally mapped to a limited region of Xp11.4. We evaluated the three families from our original study with new markers and clinically reassessed all key recombinants; we determined that the critical intervals in families 2 and 3 overlapped the RP3 locus and that a status change (from affected to probably unaffected) of a key recombinant individual in family 1 also reassigned the disease locus to include RP3 as well. Mutation analysis of the entire RPGR coding region identified two different 2-nucleotide (nt) deletions in ORF15, in family 2 (delAG) and in families 1 and 3 (delGG), both of which result in a frameshift leading to altered amino acid structure and early termination. In addition, an independent individual with X-linked cone-rod dystrophy demonstrated a 1-nt insertion (insA) in ORF15. The presence of three distinct mutations associated with the same disease phenotype provides strong evidence that mutations in RPGR exon ORF15 are responsible for COD1. Genetic heterogeneity was observed in three other families, including the identification of an in-frame 12-nt deletion polymorphism in ORF15 that did not segregate with the disease in one of these families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Exons / genetics*
  • Eye Proteins*
  • Genetic Heterogeneity
  • Genetic Linkage / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics*
  • Open Reading Frames / genetics
  • Retinitis Pigmentosa / genetics*
  • X Chromosome / genetics*


  • Carrier Proteins
  • Eye Proteins
  • RPGR protein, human

Associated data

  • GENBANK/AF286472
  • GENBANK/U57629
  • OMIM/MIM268000
  • OMIM/MIM300029
  • OMIM/MIM304202
  • OMIM/MIM312600
  • OMIM/MIM312610
  • RefSeq/NM_000328