title: Identification of the gene responsible for Best macular dystrophy.
abstract: Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration characterized by an abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. In pursuit of the disease gene, we limited the minimum genetic region by recombination breakpoint analysis and mapped to this region a novel retina-specific gene (VMD2). Genetic mapping data, identification of five independent disease-specific mutations and expression studies provide evidence that mutations within the candidate gene are a cause of BMD. The 3' UTR of the candidate gene contains a region of antisense complementarity to the 3' UTR of the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense interaction between VMD2 and FTH1 transcripts.
authors.affiliation: Department of Human Genetics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. konstantin_petrukhin@merck.com
authors.forename: K
authors.initials: K
authors.lastname: Petrukhin
authors.forename: M J
authors.initials: MJ
authors.lastname: Koisti
authors.forename: B
authors.initials: B
authors.lastname: Bakall
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.forename: T
authors.initials: T
authors.lastname: Marknell
authors.forename: O
authors.initials: O
authors.lastname: Sandgren
authors.forename: K
authors.initials: K
authors.lastname: Forsman
authors.forename: G
authors.initials: G
authors.lastname: Holmgren
authors.forename: S
authors.initials: S
authors.lastname: Andreasson
authors.forename: M
authors.initials: M
authors.lastname: Vujic
authors.forename: A A
authors.initials: AA
authors.lastname: Bergen
authors.forename: V
authors.initials: V
authors.lastname: McGarty-Dugan
authors.forename: D
authors.initials: D
authors.lastname: Figueroa
authors.forename: C P
authors.initials: CP
authors.lastname: Austin
authors.forename: M L
authors.initials: ML
authors.lastname: Metzker
authors.forename: C T
authors.initials: CT
authors.lastname: Caskey
authors.forename: C
authors.initials: C
authors.lastname: Wadelius
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000075002:Bestrophins; D017173:Caenorhabditis elegans / Q000235:genetics; D018118:Chloride Channels; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000235:genetics; D005807:Genes, Overlapping; D006801:Humans; D007473:Ion Channels; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree
chemical_list: C113133:BEST1 protein, human; C491856:Best1 protein, mouse; D000075002:Bestrophins; D018118:Chloride Channels; D018076:DNA, Complementary; D005136:Eye Proteins; D007473:Ion Channels; D005293:Ferritins