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Targeted NGS : an effective approach for molecular diagnosis of hereditary vitreoretinopathies
Author(s) -
Burin des Roziers C.,
Rothschild P.R.,
Barjol A.,
Clément C.A.,
Edelson C.,
Derrien S.,
Metge F.,
Michau S.,
Robert M.,
Prévot C.,
Dollfus H.,
Layet V.,
Delphin N.,
Bernardelli M.,
Ghiotti T.,
Hanein S.,
Fourrage C.,
Bonnefont J.P.,
Rozet J.M.,
Brézin A.,
Caputo G.,
BrémondGignac D.,
Valleix S.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.02361
Subject(s) - sanger sequencing , proband , medicine , genetics , dna sequencing , bioinformatics , mutation , biology , gene
Summary Hereditary vitreoretinopathies ( VRP s), traditionally divided into the groups of exudative and degenerative VRP s, encompass a number of diseases affecting the vitreous and the retina. These disorders are the commonest cause of inherited retinal detachment with high risk of vision loss during infancy. We designed a next generation sequencing ( NGS ) assay including ATOH 7, COL 2A1, COL 9A1, COL 9A2, COL 9A3, COL 11A1, COL 18A1, FZD 4, KCNJ 13, KIF 11, LOXL 3, LRP 5, NDP , TSPAN 12, VCAN and ZNF 408 allowing an exhaustive genetic screening with the most frequently mutated genes reported to be associated with all inherited VRP s. The diagnostic performance of this new design was evaluated on a cohort of 166 probands with a suspected clinical diagnosis of exudative or degenerative VRP s comprising 47% of children under 15 years old. We identified a large spectrum of causative mutations (single nucleotide changes as well as copy number variants) diagnosing molecular defects for 60% of the patients. Our NGS panel is therefore a promising screening method to be used efficiently in routine practice, able to detect a higher number of molecular defects than Sanger sequencing, improving significantly the molecular diagnosis of inherited VRP s.