{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":45,"searchCount":0},"additional":{"omics_type":["Unknown"],"volume":["10(9)"],"submitter":["Polla DL"],"pubmed_abstract":["Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4 Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known."],"journal":["PloS one"],"pagination":["e0138314"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4575211"],"repository":["biostudies-literature"],"pubmed_title":["Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders."],"pmcid":["PMC4575211"],"pubmed_authors":["Cardoso MT","Cardoso IC","Silva MC","Medina CT","Pogue R","de Andrade RV","Araujo R","Fernandes CC","Reis AM","Pereira RW","Polla DL"],"view_count":["45"],"additional_accession":[]},"is_claimable":false,"name":"Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders.","description":"Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4 Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015","modification":"2024-10-18T00:06:26.429Z","creation":"2019-03-26T22:56:04Z"},"accession":"S-EPMC4575211","cross_references":{"pubmed":["26380986"],"doi":["10.1371/journal.pone.0138314"]}}