The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome
Details
Serval ID
serval:BIB_93D30EAB3AFE
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome
Title of the conference
Investigative ophthalmology and visual science
Organization
ARVO E-Abstract 2324
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
50
Language
english
Abstract
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.
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.
Create date
05/02/2010 14:22
Last modification date
20/08/2019 15:56
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