Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.
Détails
ID Serval
serval:BIB_0439125ACF04
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.
Périodique
Journal of Human Genetics
ISSN
1435-232X (Electronic)
ISSN-L
1434-5161
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
56
Numéro
1
Pages
22-28
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't WOS Document Type: Article
Résumé
Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.
Mots-clé
Adolescent, Adult, Child, Codon, Nonsense/physiology, Color Vision Defects/diagnosis, Color Vision Defects/genetics, DNA Mutational Analysis, Eye Proteins/genetics, Family, Female, Genetic Association Studies, Humans, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide/physiology, Transducin/genetics, Tunisia, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/01/2011 16:15
Dernière modification de la notice
20/08/2019 12:26