BACKGROUND: @entity66 include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a @entity74 . 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 @entity66 . We screened a cohort of 101 unrelated @entity1 without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of @entity395 , Strasbourg, France, for a variety of @entity74 including @entity24251 (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and @entity8804 , isolated @entity4368 , @entity61618 and primary @entity14478 . RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated @entity1 in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of @entity1 with isolated AI (50 unrelated @entity1 ) and isolated STHAG (21 unrelated @entity1 ), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, @entity5858 mutations accounted for the majority of @entity24251 . CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of @entity66 . Furthermore, our panel will contribute to better understanding the contribution of these genes to @entity66 . TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.

A targeted next-generation sequencing assay for the molecular diagnosis of XXXX with orodental involvement.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity14478 :: ('MESH:C565114', 'Disease') :: ['failure of tooth eruption'] @entity61618 :: ('MESH:C563482', 'Disease') :: ['otodental dysplasia'] @entity66 :: ('MESH:D004194', 'Disease') :: ['orodental disease', 'orodental diseases', 'Orodental diseases'] @entity8804 :: ('MESH:D003811', 'Disease') :: ['syndromic dentinogenesis imperfecta'] @entity4368 :: ('MESH:D003805', 'Disease') :: ['dentin dysplasia'] @entity5858 :: ('1308', 'Gene') :: ['COL17A1'] @entity24251 :: ('MESH:D000567', 'Disease') :: ['autosomal-dominant AI cases', 'isolated and syndromic amelogenesis imperfecta'] @entity74 :: ('MESH:D030342', 'Disease') :: ['orodental disorders', 'genetic syndrome'] @entity395 :: ('MESH:D035583', 'Disease') :: ['Rare Diseases']
@entity74 :: (MESH:D030342,Disease) :: ['genetic disorders']
