Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa

Lori S. Sullivan, John R. Heckenlively, Sara J. Bowne, Jian Zuo, Winston A. Hide, Andreas Gal, Michael Denton, Chris F. Inglehearn, Susan H Blanton, Stephen P. Daiger

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of I in 3,500 individuals worldwide. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina- specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.

Original languageEnglish
Pages (from-to)255-259
Number of pages5
JournalNature Genetics
Volume22
Issue number3
DOIs
StatePublished - Jul 1 1999
Externally publishedYes

Fingerprint

Retinitis Pigmentosa
Retina
Retinal Diseases
Mutation
Nonsense Codon
Codon
Genes
Lissencephaly
Night Blindness
Vision Disorders
Blindness
Heterozygote
Visual Fields
Young Adult
Chromosomes
Amino Acids
Bone and Bones
Incidence
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Sullivan, L. S., Heckenlively, J. R., Bowne, S. J., Zuo, J., Hide, W. A., Gal, A., ... Daiger, S. P. (1999). Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. Nature Genetics, 22(3), 255-259. https://doi.org/10.1038/10314

Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. / Sullivan, Lori S.; Heckenlively, John R.; Bowne, Sara J.; Zuo, Jian; Hide, Winston A.; Gal, Andreas; Denton, Michael; Inglehearn, Chris F.; Blanton, Susan H; Daiger, Stephen P.

In: Nature Genetics, Vol. 22, No. 3, 01.07.1999, p. 255-259.

Research output: Contribution to journalArticle

Sullivan, LS, Heckenlively, JR, Bowne, SJ, Zuo, J, Hide, WA, Gal, A, Denton, M, Inglehearn, CF, Blanton, SH & Daiger, SP 1999, 'Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa', Nature Genetics, vol. 22, no. 3, pp. 255-259. https://doi.org/10.1038/10314
Sullivan LS, Heckenlively JR, Bowne SJ, Zuo J, Hide WA, Gal A et al. Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. Nature Genetics. 1999 Jul 1;22(3):255-259. https://doi.org/10.1038/10314
Sullivan, Lori S. ; Heckenlively, John R. ; Bowne, Sara J. ; Zuo, Jian ; Hide, Winston A. ; Gal, Andreas ; Denton, Michael ; Inglehearn, Chris F. ; Blanton, Susan H ; Daiger, Stephen P. / Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. In: Nature Genetics. 1999 ; Vol. 22, No. 3. pp. 255-259.
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