Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta

  • Am J Hum Genet. 2009 Feb;84(2):259-65. doi: 10.1016/j.ajhg.2009.01.006.
Bozena Polok  1 ,  Pascal Escher ,  Aude Ambresin ,  Eliane Chouery ,  Sylvain Bolay ,  Isabelle Meunier ,  Francis Nan ,  Christian Hamel ,  Francis L Munier ,  Bernard Thilo ,  André Mégarbané ,  Daniel F Schorderet
Affiliations
  • 1. Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland.
PMID: 19200527 DOI: 10.1016/j.ajhg.2009.01.006
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.