Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta.
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.
Polok
Bozena
B
Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland.
Escher
Pascal
P
Ambresin
Aude
A
Chouery
Eliane
E
Bolay
Sylvain
S
Meunier
Isabelle
I
Nan
Francis
F
Hamel
Christian
C
Munier
Francis L
FL
Thilo
Bernard
B
Mégarbané
André
A
Schorderet
Daniel F
DF
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
C539261:CNNM4 protein, human; D027682:Cation Transport Proteins