Back to Search
Start Over
A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.
- Source :
-
Journal of medical genetics [J Med Genet] 2016 Feb; Vol. 53 (2), pp. 98-110. Date of Electronic Publication: 2015 Oct 26. - Publication Year :
- 2016
-
Abstract
- 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.<br />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.<br />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.<br />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.<br />Trial Registration Numbers: NCT01746121 and NCT02397824.<br /> (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Subjects :
- Amelogenesis Imperfecta genetics
Autoantigens genetics
Chromosome Deletion
Chromosome Disorders genetics
Chromosomes, Human, Pair 11 genetics
Cohort Studies
Coloboma genetics
Dentin Dysplasia genetics
France
Hearing Loss, Sensorineural genetics
Humans
Non-Fibrillar Collagens genetics
Reproducibility of Results
Collagen Type XVII
High-Throughput Nucleotide Sequencing methods
Mutation
Tooth Abnormalities genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1468-6244
- Volume :
- 53
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 26502894
- Full Text :
- https://doi.org/10.1136/jmedgenet-2015-103302