Identification of novel rhodopsin mutations responsible for retinitis pigmentosa: implications for the structure and function of rhodopsin

Jennifer P. Macke, Carol M. Davenport, Samuel G. Jacobson, Jill C. Hennessey, Federico Gonzalez-Fernandez, Brian P. Conway, John Heckenlively, Rosalind Palmer, Irene H. Maumenee, Paul Sieving, Peter Gouras, William Good, Jeremy Nathans

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93 Scopus citations


Ten rhodopsin mutations have been found in a screen of 282 subjects with retinitis pigmentosa (RP), 76 subjects with Leber congenital amaurosis, and 3 subjects with congenital stationary night blindness. Eight of these mutations (gly51-to-ala, val104-to-ile, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, val209-to-met, and his211-to-arg) produce amino acid substitutions, one (gln64-to-ter) introduces a stop codon, and one changes a guanosine in the intron 4 consensus splice donor sequence to thymidine. Cosegregation of RP with gln64-to-ter, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, his211-to-arg, and the splice site guanosine-to-thymidine indicates that these mutations are likely to cause retinal disease. Val104-to-ile does not cosegregate and is therefore unlikely to be related to retinal disease. The relevance of gly51-to-ala and val209-to-met remains to be determined. The finding of gln64-to-ter in a family with autosomal dominant RP is in contrast to a recent report of a recessive disease phenotype associated with the rhodopsin mutation glu249-to-ter. In the present screen, all of the mutations that cosegregate with retinal disease were found among patients with RP. The mutations described here bring to 35 the total number of amino acid substitutions identified thus far in rhodopsin that are associated with RP. The distribution of the substitutions along the polypeptide chain is significantly nonrandom: 63% of the substitutions involve those 19% of amino acids that are identical among vertebrate visual pigments sequenced to date.

Original languageEnglish (US)
Pages (from-to)80-89
Number of pages10
JournalAmerican journal of human genetics
Issue number1
StatePublished - Jul 1993

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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