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Journal Articles Journal of Medical Genetics Year : 2016

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement

1 LGM - Laboratoire de Génétique Médicale
2 FMTS - Fédération de Médecine Translationnelle de Strasbourg
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
4 Les Hôpitaux Universitaires de Strasbourg (HUS)
5 UNISTRA - Université de Strasbourg
6 Evolution Paris Seine
7 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
8 CHU Nice - Centre Hospitalier Universitaire de Nice
9 URB2i (URP_4462) - Unité de Recherche Biomatériaux Innovants et Interfaces
10 Service d’Odontologie Conservatrice et Pédiatrique [CHU Nantes]
11 Heidelberg University
12 HCL - Hospices Civils de Lyon
13 UCBL - Université Claude Bernard Lyon 1
14 Service de génétique clinique [Rennes]
15 UT3 - Université Toulouse III - Paul Sabatier
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 CHU Lille
18 CHU Nantes - Centre hospitalier universitaire de Nantes
19 Nantes Univ - Nantes Université
20 Service de génétique [Tours]
21 UNSA - Université de Nice Sophia-Antipolis
22 Nouvel Hôpital Civil de Strasbourg
23 HUS - Les Hôptaux universitaires de Strasbourg
24 UM5 - Université Mohammed V de Rabat [Agdal]
25 CHU Lyon
26 CHU Strasbourg
27 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
28 CH E.Muller Mulhouse - Centre Hospitalier Emile Muller [Mulhouse]
29 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
30 MAFACE - Centre de Référence des Maladies Rares de la Face et de la Cavité Buccale
31 CHU Rothschild [AP-HP]
32 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
33 TIMONE - Hôpital de la Timone [CHU - APHM]
34 Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
35 Faculté de chirurgie dentaire - Strasbourg
Barbara Gasse
  • Function : Author
  • PersonId : 970839
Jean-Luc Davideau
Ute Moog
  • Function : Author
  • PersonId : 887755
Monique Marie Rousset
  • Function : Author
Annick Toutain
Nathalie Guffon
  • Function : Author
Anne Dieux
  • Function : Author
Bérénice Doray
  • Function : Author
Yves Alembik
  • Function : Author


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
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Origin : Publication funded by an institution

Dates and versions

hal-01272929 , version 1 (17-06-2022)



Megana K. Prasad, Véronique Geoffroy, Serge Vicaire, Bernard Jost, Michael Dumas, et al.. A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement. Journal of Medical Genetics, 2016, 53 (2), pp.98--110. ⟨10.1136/jmedgenet-2015-103302⟩. ⟨hal-01272929⟩
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