Polok Bozena, Escher Pascal, Ambresin Aude, Chouery Eliane, Bolay Sylvain, Meunier Isabelle, Nan Francis, Hamel Christian, Munier Francis L, Thilo Bernard, Mégarbané André, Schorderet Daniel F
Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland.
Am J Hum Genet. 2009 Feb;84(2):259-65. doi: 10.1016/j.ajhg.2009.01.006. Epub 2009 Feb 5.
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.
视锥-视杆营养不良是视网膜的遗传性营养不良，其特征是沉积物主要积聚在眼部富含视锥细胞的黄斑区域。营养不良可能局限于视网膜，也可能是综合征的一部分。与非综合征性视锥-视杆营养不良不同，综合征性视锥-视杆营养不良在基因上是异质性的，编码结构、细胞粘附和转运蛋白的基因发生突变。我们使用全基因组单核苷酸多态性（SNP）单倍型分析来精细定位该基因座，并采用候选基因方法，在古老保守结构域蛋白4基因（CNNM4）中鉴定出纯合突变，这些突变要么产生截短蛋白，要么发生在该蛋白的高度保守区域。鉴于CNNM4与金属离子转运有关，视锥-视杆营养不良和牙釉质发育不全可能源于异常的离子稳态。
