RT Journal Article
SR Electronic
T1 A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 98
OP 110
DO 10.1136/jmedgenet-2015-103302
VO 53
IS 2
A1 Megana K Prasad
A1 Véronique Geoffroy
A1 Serge Vicaire
A1 Bernard Jost
A1 Michael Dumas
A1 Stéphanie Le Gras
A1 Marzena Switala
A1 Barbara Gasse
A1 Virginie Laugel-Haushalter
A1 Marie Paschaki
A1 Bruno Leheup
A1 Dominique Droz
A1 Amelie Dalstein
A1 Adeline Loing
A1 Bruno Grollemund
A1 Michèle Muller-Bolla
A1 Séréna Lopez-Cazaux
A1 Maryline Minoux
A1 Sophie Jung
A1 Frédéric Obry
A1 Vincent Vogt
A1 Jean-Luc Davideau
A1 Tiphaine Davit-Beal
A1 Anne-Sophie Kaiser
A1 Ute Moog
A1 Béatrice Richard
A1 Jean-Jacques Morrier
A1 Jean-Pierre Duprez
A1 Sylvie Odent
A1 Isabelle Bailleul-Forestier
A1 Monique Marie Rousset
A1 Laure Merametdijan
A1 Annick Toutain
A1 Clara Joseph
A1 Fabienne Giuliano
A1 Jean-Christophe Dahlet
A1 Aymeric Courval
A1 Mustapha El Alloussi
A1 Samir Laouina
A1 Sylvie Soskin
A1 Nathalie Guffon
A1 Anne Dieux
A1 Bérénice Doray
A1 Stephanie Feierabend
A1 Emmanuelle Ginglinger
A1 Benjamin Fournier
A1 Muriel de la Dure Molla
A1 Yves Alembik
A1 Corinne Tardieu
A1 François Clauss
A1 Ariane Berdal
A1 Corinne Stoetzel
A1 Marie Cécile Manière
A1 Hélène Dollfus
A1 Agnès Bloch-Zupan
YR 2016
UL http://jmg.bmj.com/content/53/2/98.abstract
AB Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders.Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption.Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases.Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease.Trial registration numbers NCT01746121 and NCT02397824.