NGS-Based Clinical Diagnosis of Genetically Heterogeneous Disorders

  • C. A. Valencia
  • T. A. Sivakumaran
  • B. T. Tinkle
  • A. Husami
  • K. Zhang


Next-generation sequencing (NGS) has transformed genomic research by decreasing the cost of sequencing and increasing the throughput. NGS platforms have evolved to provide an accurate and comprehensive means for the detection of molecular mutations, and the recent focus is on using NGS technology in clinical diagnosis. NGS analysis has three major components: enrichment, sequencing, and analysis. In the last several years, enrichment technologies based on hybridization or amplification principles have emerged. Similarly, sequencing platforms have continued to improve by increasing the sequencing output and decreasing the sequencing time and cost. Various enrichment and sequencing platform combinations have been utilized for the diagnosis of genetically heterogeneous disorders, and it is the topic of discussion for this chapter. We describe the employment of NGS approaches to the diagnosis of genetically heterogeneous disorders and mention advantages and challenges of these technologies in a clinical laboratory setting.


Hearing Loss Retinitis Pigmentosa Arrhythmogenic Right Ventricular Cardiomyopathy Primary Ciliary Dyskinesia Brugada Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Atrial fibrillation


Arrayed primer extension


Autosomal recessive polycystic kidney disease


Arrhythmogenic right ventricular cardiomyopathy


Bardet–Biedl syndrome


Congenital heart disease


Congenital hepatic fibrosis


Congenital muscular dystrophy


Central nervous system


Conduction system disease


Dilated cardiomyopathy




Hypertrophic cardiomyopathy


Hemophagocytic lymphohistiocytosis


Joubert syndrome-related disorders


Leber congenital amaurosis


Limb-girdle muscular dystrophy type 1B


Left ventricular noncompaction


Merosin-deficient congenital muscular dystrophy


Congenital muscular dystrophy type 1C


Muscle-eye-brain disease


Meckel–Gruber syndrome


Next-generation sequencing




Nephronophthisis-associated ciliopathies


Primary ciliary dyskinesia


Primary immunodeficiency disorders


Retinitis pigmentosa


Rigid spine syndrome


Sudden cardiac death


Supraventricular tachycardia


Ventricular tachycardia


Whole genome amplification


Walker–Warburg syndrome


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • C. A. Valencia
    • 1
    • 2
  • T. A. Sivakumaran
    • 1
    • 2
  • B. T. Tinkle
    • 1
    • 2
  • A. Husami
    • 1
    • 2
  • K. Zhang
    • 1
    • 2
  1. 1.Division of Human GeneticsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of PediatricsUniversity of Cincinnati Medical SchoolCincinnatiUSA

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