Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing

Jun Seok Bae, Nayoung K.D. Kim, Chung Lee, Sang Cheol Kim, Hey Ran Lee, Hae Ryong Song, Kun Bo Park, Hyun Woo Kim, Soon-Hyuck Lee, Ha Yong Kim, Soon Chul Lee, Changhoon Jeong, Moon Seok Park, Won Joon Yoo, Chin Youb Chung, In Ho Choi, Ok Hwa Kim, Woong Yang Park, Tae Joon Cho

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)563-569
Number of pages7
JournalGenetics in Medicine
Issue number6
Publication statusPublished - 2016 Jun 1


  • Mendelian
  • molecular genetic test
  • monogenic
  • nextgeneration sequencing
  • skeletal dysplasia

ASJC Scopus subject areas

  • Genetics(clinical)


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