title: Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing.
abstract: The purpose of this study was to evaluate the clinical utility of targeted exome sequencing (TES) as a molecular diagnostic tool for patients with skeletal dysplasia.
  
  
  
  A total of 185 patients either diagnosed with or suspected to have skeletal dysplasia were recruited over a period of 3 years. TES was performed for 255 genes associated with the pathogenesis of skeletal dysplasia, and candidate variants were selected using a bioinformatics analysis. All candidate variants were confirmed by Sanger sequencing, correlation with the phenotype, and a cosegregation study in the family.
  
  
  
  TES detected "confirmed" or "highly likely" pathogenic sequence variants in 74% (71 of 96) of cases in the assured clinical diagnosis category and 20.3% (13 of 64 cases) of cases in the uncertain clinical diagnosis category. TES successfully detected pathogenic variants in all 25 cases of previously known genotypes. The data also suggested a copy-number variation that led to a molecular diagnosis.
  
  
  
  This study demonstrates the feasibility of TES for the molecular diagnosis of skeletal dysplasia. However, further confirmation is needed for a final molecular diagnosis, including Sanger sequencing of candidate variants with suspected, poorly captured exons.Genet Med 18 6, 563-569.
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Nayoung K D
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Chung
authors.initials: C
authors.lastname: Lee
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hey Ran
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Korea University Guro Hospital, Seoul, Korea.
authors.forename: Hae-Ryong
authors.initials: HR
authors.lastname: Song
authors.affiliation: Department of Orthopaedic Surgery, Inje University Haeundae Hospital, Busan, Korea.
authors.forename: Kun Bo
authors.identifier: 0000-0002-8839-4870
authors.initials: KB
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Soon Hyuck
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Eulji University Daejeon Hospital, Daejeon, Korea.
authors.forename: Ha Yong
authors.identifier: 0000-0003-4949-9212
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Bucheon St. Mary's Hospital, the Catholic University of Korea, Bucheon, Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Jeong
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Won Joon
authors.identifier: 0000-0001-5225-1440
authors.initials: WJ
authors.lastname: Yoo
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Chin Youb
authors.initials: CY
authors.lastname: Chung
authors.affiliation: Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Choi
authors.affiliation: Department of Radiology, Woorisoa Children's Hospital, Seoul, Korea.
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Woong-Yang
authors.identifier: 0000-0003-4234-0380
authors.initials: WY
authors.lastname: Park
authors.affiliation: Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Tae-Joon
authors.identifier: 0000-0001-8514-377X
authors.initials: TJ
authors.lastname: Cho
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D057089:Pathology, Molecular; D010375:Pedigree; D010641:Phenotype; D000073359:Exome Sequencing / Q000379:methods*