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Open Access 01-12-2015 | Research

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Authors: Elise Boulanger-Scemama, Said El Shamieh, Vanessa Démontant, Christel Condroyer, Aline Antonio, Christelle Michiels, Fiona Boyard, Jean-Paul Saraiva, Mélanie Letexier, Eric Souied, Saddek Mohand-Saïd, José-Alain Sahel, Christina Zeitz, Isabelle Audo

Published in: Orphanet Journal of Rare Diseases | Issue 1/2015

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.

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Title: Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation
Authors: Elise Boulanger-Scemama
Said El Shamieh
Vanessa Démontant
Christel Condroyer
Aline Antonio
Christelle Michiels
Fiona Boyard
Jean-Paul Saraiva
Mélanie Letexier
Eric Souied
Saddek Mohand-Saïd
José-Alain Sahel
Christina Zeitz
Isabelle Audo
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2015
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-015-0300-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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