title: Clinical application of next-generation sequencing for Mendelian diseases.
abstract: Over the past decade, next-generation sequencing (NGS) has led to an exponential increase in our understanding of the genetic basis of Mendelian diseases. NGS allows for the analysis of multiple regions of the genome in one single reaction and has been shown to be a cost-effective and efficient tool in investigating patients with Mendelian diseases. More recently, NGS has been successfully deployed in the clinics, with a reported diagnostic yield of ~25 %. However, recommendations on clinical implementation of NGS are still evolving with numerous key challenges that impede the widespread use of genetics in everyday medicine. These challenges include when to order, on whom to order, what type of test to order, and how to interpret and communicate the results, including incidental findings, to the patient and family. In this review, we discuss these challenges and suggest guidelines on implementing NGS in the routine clinical workflow.
authors.affiliation: Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.|Paediatrics Academic Clinical Programme, SingHealth Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Saumya Shekhar
authors.initials: SS
authors.lastname: Jamuar
authors.affiliation: Paediatrics Academic Clinical Programme, SingHealth Duke-NUS Graduate Medical School, Singapore, Singapore. tanec@bigfoot.com.|KK Research Centre, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore, Singapore. tanec@bigfoot.com.
authors.forename: Ene-Choo
authors.initials: EC
authors.lastname: Tan
mesh_terms: D035843:Biomedical Research; D059472:Exome / Q000235:genetics*; D030342:Genetic Diseases, Inborn; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009154:Mutation; D017422:Sequence Analysis, DNA