The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome

Schorderet, D.F.; Polok, B.; Escher, Pascal; Favez, T.; Voirol, N.; Bolay, S.; Ambresin, A.; Hamel, C.; Mégarbane, A.; Munier, F.L. (2009). The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome. In: Investigative ophthalmology and visual science 50. ARVO E-Abstract 2324

Purpose:To identify the gene causing rod-cone dystrophy/amelogenesis imperfecta
Methods:Homozygosity mapping was performed using the Affymetrix 50K XbaI array in one family and candidate genes in the linked interval were sequenced with ABI Dye Terminator, vers. 1 in the index patient of 3 families. The identified mutations were screened in normal control individuals. Expression analyses were performed on RNA extracted from the brain, various parts of the eye and teeth; immunostaining was done on mouse eyes and jaw and knock-down experiments were carried out in zebrafish embroys.
Results:Sequencing the coding regions of ancient conserved domain protein 4 (CNNM4), a metal ions transporter, revealed a 1-base pair duplication (p.L438fs) in family A, a p.R236Q mutation in family B and a p.L324P in family C. All these mutations were homozygous and involved very conserved amino acids in paralogs and orthologs. Immunostaining and RT-PCR confirmed that CNNM4 was strongly expressed in various parts of the eye and in the teeth. Morpholino experiments in zebrafish showed a loss of ganglion cells at 5 days post fertilization.
Conclusions:The rod-cone dystrophy/amelogenesis imperfecta syndrome is caused by mutation in CNNM4 and is due to aberrant metal ion homeostasis.

Item Type:

Conference or Workshop Item (Abstract)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal


600 Technology > 610 Medicine & health


ARVO E-Abstract 2324




Pascal Escher

Date Deposited:

11 Jul 2017 09:32

Last Modified:

05 Dec 2022 15:06


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