Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness

Détails

ID Serval
serval:BIB_F7BF23FFFFA7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness
Périodique
American Journal of Human Genetics
Auteur(s)
Zeitz  C., Kloeckener-Gruissem  B., Forster  U., Kohl  S., Magyar  I., Wissinger  B., Matyas  G., Borruat  F. X., Schorderet  D. F., Zrenner  E., Munier  F. L., Berger  W.
ISSN
0002-9297 (Print)
Statut éditorial
Publié
Date de publication
10/2006
Volume
79
Numéro
4
Pages
657-67
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
Mutations in genes encoding either components of the phototransduction cascade or proteins presumably involved in signaling from photoreceptors to adjacent second-order neurons have been shown to cause congenital stationary night blindness (CSNB). Sequence alterations in CACNA1F lead to the incomplete type of CSNB (CSNB2), which can be distinguished by standard electroretinography (ERG). CSNB2 is associated with a reduced rod b-wave, a substantially reduced cone a-wave, and a reduced 30-Hz flicker ERG response. CACNA1F encodes the alpha 1-subunit of an L-type Ca2+ channel (Cav1.4 alpha ), which is specific to photoreceptors and is present at high density in the synaptic terminals. Ten of our patients with CSNB2 showed no mutation in CACNA1F. To identify the disease-causing mutations, we used a candidate-gene approach. CABP4, a member of the calcium-binding protein (CABP) family, is located in photoreceptor synaptic terminals and is directly associated with the C-terminal domain of the Cav1.4 alpha . Mice lacking either Cabp4 or Cav1.4 alpha display a CSNB2-like phenotype. Here, we report for the first time that mutations in CABP4 lead to autosomal recessive CSNB. Our studies revealed homozygous and compound heterozygous mutations in two families. We also show that these mutations reduce the transcript levels to 30%-40% of those in controls. This suggests that the reduced amount of CABP4 is the reason for the signaling defect in these patients.
Mots-clé
Adolescent Adult Amino Acid Sequence Calcium Channels, L-Type/genetics Calcium-Binding Proteins/chemistry/*genetics Chromosomes, Human, Pair 11 Electroretinography Exons Female Gene Deletion *Genes, Recessive Humans Male Middle Aged Molecular Sequence Data *Mutation Mutation, Missense Night Blindness/congenital/*genetics/physiopathology Pedigree Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Visual Acuity
Pubmed
Web of science
Création de la notice
28/01/2008 13:59
Dernière modification de la notice
03/03/2018 22:50
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