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Molecular Diagnosis of Congenital Disorders of Glycosylation (CDG)

Chapter

Abstract

Glycosylation is the addition of sugars (glycans) to proteins and lipids. Defective synthesis, assembly, or processing of glycans results in a group of disorders known as congenital disorders of glycosylation (CDG). Next-generation sequencing (NGS) technology is used in many molecular diagnostic laboratories and consists of comprehensive panels of genes associated with particular disorders and whole exome sequencing (WES) which has recently debuted in the diagnostic laboratory. Cautions and challenges with using NGS panels and WES in the clinical setting using CDG as an example are discussed. A comprehensive NGS panel for CDG is being used when there is no indication either biochemically or clinically what gene defect may be present. In the research setting, WES was successfully used to identify the gene defect in several individuals with unknown types of CDG. New gene discoveries for CDG are leading to improved molecular diagnostic testing for CDG, including an updated comprehensive NGS panel. Identification of new CDG genes also provides direction for translational research, which is already occurring for several subtypes of CDG.

Keywords

Gene Defect Whole Exome Sequencing Clinical Laboratory Improvement Amendment PMM2 Gene Specific Gene Defect 
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.

Abbreviations

HGMD

Human Gene Mutation Database

OMIM

Online Mendelian Inheritance of Man

WES

Whole exome sequencing

CDG

Congenital disorders of glycosylation

NGS

Next-generation sequencing

GPI

Glycophosphatidylinositol

IEF

Isoelectric focusing

MS

Mass spectrometry

CAP

College of American Pathologists

CLIA

Clinical Laboratory Improvement Amendments

HIPAA

Health Insurance Portability and Accountability Act

OST

Oligosaccharyltransferase complex

VOUS

Variant of unknown clinical significance

NHLBI

National Heart, Lung, and Blood Institute

CGH

Comparative genomic hybridization

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Human GeneticsEmory University School of MedicineAtlantaUSA
  2. 2.Whitehead Biomedical Research BuildingEmory University School of MedicineAtlantaUSA

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