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ABSTRACT: Background
Cone and cone-rod dystrophies are clinically and genetically heterogeneous inherited retinal disorders with predominant cone impairment. They should be distinguished from the more common group of rod-cone dystrophies (retinitis pigmentosa) due to their more severe visual prognosis with early central vision loss. The purpose of our study was to document mutation spectrum of a large French cohort of cone and cone-rod dystrophies.Methods
We applied Next-Generation Sequencing targeting a panel of 123 genes implicated in retinal diseases to 96 patients. A systematic filtering approach was used to identify likely disease causing variants, subsequently confirmed by Sanger sequencing and co-segregation analysis when possible.Results
Overall, the likely causative mutations were detected in 62.1 % of cases, revealing 33 known and 35 novel mutations. This rate was higher for autosomal dominant (100 %) than autosomal recessive cases (53.8 %). Mutations in ABCA4 and GUCY2D were responsible for 19.2 % and 29.4 % of resolved cases with recessive and dominant inheritance, respectively. Furthermore, unexpected genotype-phenotype correlations were identified, confirming the complexity of inherited retinal disorders with phenotypic overlap between cone-rod dystrophies and other retinal diseases.Conclusions
In summary, this time-efficient approach allowed mutation detection in the most important cohort of cone-rod dystrophies investigated so far covering the largest number of genes. Association of known gene defects with novel phenotypes and mode of inheritance were established.
SUBMITTER: Boulanger-Scemama E
PROVIDER: S-EPMC4566196 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Boulanger-Scemama Elise E El Shamieh Said S Démontant Vanessa V Condroyer Christel C Antonio Aline A Michiels Christelle C Boyard Fiona F Saraiva Jean-Paul JP Letexier Mélanie M Souied Eric E Mohand-Saïd Saddek S Sahel José-Alain JA Zeitz Christina C Audo Isabelle I
Orphanet journal of rare diseases 20150624
<h4>Background</h4>Cone and cone-rod dystrophies are clinically and genetically heterogeneous inherited retinal disorders with predominant cone impairment. They should be distinguished from the more common group of rod-cone dystrophies (retinitis pigmentosa) due to their more severe visual prognosis with early central vision loss. The purpose of our study was to document mutation spectrum of a large French cohort of cone and cone-rod dystrophies.<h4>Methods</h4>We applied Next-Generation Sequenc ...[more]