A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy

Nat Genet. 2001 Jan;27(1):89-93. doi: 10.1038/83817.

Abstract

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Exons / genetics
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Female
  • Genes, Dominant / genetics*
  • Humans
  • In Situ Hybridization
  • Introns / genetics
  • Lod Score
  • Macaca mulatta / genetics
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Pedigree
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Retina / metabolism
  • Retina / pathology
  • Sequence Alignment
  • Sequence Deletion / genetics*

Substances

  • ELOVL4 protein, human
  • Elovl4 protein, mouse
  • Eye Proteins
  • Membrane Proteins
  • RNA, Messenger

Associated data

  • GENBANK/AF277093
  • GENBANK/AF277094
  • GENBANK/AF279649
  • GENBANK/AF279650
  • GENBANK/AF279651
  • GENBANK/AF279652
  • GENBANK/AF279653
  • GENBANK/AF279654
  • GENBANK/AL132875