Null RPGRIP1 alleles in patients with Leber congenital amaurosis

Am J Hum Genet. 2001 May;68(5):1295-8. doi: 10.1086/320113. Epub 2001 Mar 29.


We isolated and characterized the entire coding sequence of a human gene encoding a protein that interacts with RPGR, a protein that is absent or mutant in many cases of X-linked retinitis pigmentosa. The newly identified gene, called "RPGRIP1" for RPGR-interacting protein (MIM 605446), is located within 14q11, and it encodes a protein predicted to contain 1,259 amino acids. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone photoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Female
  • Gene Deletion*
  • Genes, Recessive / genetics
  • Genotype
  • Humans
  • Male
  • Molecular Sequence Data
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Proteins / genetics*


  • Cytoskeletal Proteins
  • Proteins
  • RPGRIP1 protein, human