title: Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta.
abstract: Cone-rod dystrophies are inherited dystrophies of the retina characterized by the accumulation of deposits mainly localized to the cone-rich macular region of the eye. Dystrophy can be limited to the retina or be part of a syndrome. Unlike nonsyndromic cone-rod dystrophies, syndromic cone-rod dystrophies are genetically heterogeneous with mutations in genes encoding structural, cell-adhesion, and transporter proteins. Using a genome-wide single-nucleotide polymorphism (SNP) haplotype analysis to fine map the locus and a gene-candidate approach, we identified homozygous mutations in the ancient conserved domain protein 4 gene (CNNM4) that either generate a truncated protein or occur in highly conserved regions of the protein. Given that CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis.
authors.affiliation: Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Polok
authors.forename: Pascal
authors.initials: P
authors.lastname: Escher
authors.forename: Aude
authors.initials: A
authors.lastname: Ambresin
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bolay
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.forename: Francis
authors.initials: F
authors.lastname: Nan
authors.forename: Christian
authors.initials: C
authors.lastname: Hamel
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.forename: Bernard
authors.initials: B
authors.lastname: Thilo
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C539261:CNNM4 protein, human; D027682:Cation Transport Proteins