title: Clinical Diagnosis of Mendelian Disorders Using a Comprehensive Gene-Targeted Panel Test for Next-Generation Sequencing.
abstract: BACKGROUND
  Genetic diagnoses provide beneficial information to patients and families. However, traditional genetic diagnoses are often difficult even for experienced clinicians and require recognition of characteristic patterns of signs or symptoms to guide targeted genetic testing for the confirmation of diagnoses. Next-generation sequencing (NGS) is a powerful genetic diagnostic tool. However, whole-genome and whole-exome sequencing (WES) are expensive, and the interpretation of results is difficult. Hence, target gene capture sequencing of gene panels has recently been applied to genetic diagnoses. Herein, we demonstrate that targeted sequencing approaches using gene panel testing are highly efficient for the diagnosis of Mendelian disorders.
  
  
  METHODS
  NGS using TruSight one gene panel was performed in 17 families and 20 patients, and we developed a bioinformatic pipeline at our institution for detecting mutations.
  
  
  RESULTS
  We detected causative mutations in 6 of 17 (35%) families. In particular, 11 (65%) families had syndromic diagnosis and 6 (35%) had no syndromic diagnosis before NGS testing. The number of positive diagnoses was 5 of 11 (45%) in the syndromic group and were 1 of 6 (17%) among patients of the no syndromic diagnosis group.
  
  
  CONCLUSIONS
  Diagnostic yields in the present study were higher than in previous reports of genetic and chromosomal tests and WES. The present comprehensive gene-targeted panel test is a powerful diagnostic tool for Mendelian disorders.
authors: Division of Child Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683-8504, Japan; †Division of Clinical Genetics, Tottori University Hospital, Yonago 683-8504, Japan.
authors: Tetsuya
authors: T
authors: Okazaki
authors: ‡Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago 683-8503, Japan.
authors: Megumi
authors: M
authors: Murata
authors: §Division of Technical Department, Tottori University, Yonago 683-8503, Japan.
authors: Masachika
authors: M
authors: Kai
authors: ‡Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago 683-8503, Japan.
authors: Kaori
authors: K
authors: Adachi
authors: †Division of Clinical Genetics, Tottori University Hospital, Yonago 683-8504, Japan; ‖Center for Promoting Next-Generation Highly Advanced Medicine, Tottori University Hospital, Yonago 683-8504, Japan.
authors: Naoko
authors: N
authors: Nakagawa
authors: †Division of Clinical Genetics, Tottori University Hospital, Yonago 683-8504, Japan; ¶Department of Fundamental Nursing, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Noriko
authors: N
authors: Kasagi
authors: Division of Child Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683-8504, Japan; †Division of Clinical Genetics, Tottori University Hospital, Yonago 683-8504, Japan.
authors: Wataru
authors: W
authors: Matsumura
authors: Division of Child Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
authors: Yoshihiro
authors: Y
authors: Maegaki
authors: †Division of Clinical Genetics, Tottori University Hospital, Yonago 683-8504, Japan; ‡Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago 683-8503, Japan; ‖Center for Promoting Next-Generation Highly Advanced Medicine, Tottori University Hospital, Yonago 683-8504, Japan.
authors: Eiji
authors: E
authors: Nanba
keywords: candidate gene analyses; diagnosis high-throughput DNA sequencing