title: A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy.
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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Kniazeva
authors.forename: M
authors.initials: M
authors.lastname: Han
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: M L
authors.initials: ML
authors.lastname: Metzker
authors.forename: R
authors.initials: R
authors.lastname: Allikmets
authors.forename: D J
authors.initials: DJ
authors.lastname: Zack
authors.forename: L E
authors.initials: LE
authors.lastname: Kakuk
authors.forename: P S
authors.initials: PS
authors.lastname: Lagali
authors.forename: P W
authors.initials: PW
authors.lastname: Wong
authors.forename: I M
authors.initials: IM
authors.lastname: MacDonald
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
authors.forename: D J
authors.initials: DJ
authors.lastname: Figueroa
authors.forename: C P
authors.initials: CP
authors.lastname: Austin
authors.forename: R J
authors.initials: RJ
authors.lastname: Gould
authors.forename: R
authors.initials: R
authors.lastname: Ayyagari
authors.forename: K
authors.initials: K
authors.lastname: Petrukhin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns / Q000235:genetics; D008126:Lod Score; D008253:Macaca mulatta / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012160:Retina / Q000378:metabolism / Q000473:pathology; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C418975:ELOVL4 protein, human; C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger