|Title:||Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin||Authors:||Wang J.
|Issue Date:||2013||Journal Volume:||15||Journal Issue:||2||Start page/Pages:||106-114||Source:||Genetics in Medicine||Abstract:||
Purpose:Glycogen storage diseases are a group of inborn errors of glycogen synthesis or catabolism. The outcome for untreated patients can be devastating. Given the genetic heterogeneity and the limited availability of enzyme study data, the definitive diagnosis of glycogen storage diseases is made on the basis of sequence analysis of selected potentially causative genes.Methods:A massively parallel sequencing test was developed for simultaneous sequencing of 16 genes known to cause muscle and liver forms of glycogen storage diseases: GYS2, GYS1, G6PC, SLC37A4, GAA, AGL, GBE1, PYGM, PYGL, PFKM, PHKA2, PHKB, PHKG2, PHKA1, PGAM2, and PGM1. All the nucleotides in the coding regions of these 16 genes have been enriched with sufficient coverage in an unbiased manner.Results:Massively parallel sequencing demonstrated 100% sensitivity and specificity as compared with Sanger sequencing. Massively parallel sequencing correctly identified all types of mutations, including single-nucleotide substitutions, small deletions and duplications, and large deletions involving one or more exons. In addition, we have confirmed the molecular diagnosis in 11 of 17 patients in whom glycogen storage diseases were suspected.Conclusion:This report demonstrates the clinical utility of massively parallel sequencing technology in the diagnostic testing of a group of clinically and genetically heterogeneous disorders such as glycogen storage diseases, in a cost-and time-efficient manner. ? American College of Medical Genetics and Genomics.
|ISSN:||1098-3600||DOI:||10.1038/gim.2012.104||SDG/Keyword:||nucleotide derivative; adolescent; adult; AGL gene; article; child; clinical article; exon; female; G6PC gene; Gaa gene; GBE1 gene; gene; gene deletion; gene duplication; gene mutation; gene sequence; genetic heterogeneity; glycogen storage disease; GYS1 gene; GYS2 gene; human; infant; male; massively parallel sequencing; molecular diagnosis; molecular genetics; Pfkm gene; PGAM2 gene; PGM1 gene; PHKA1 gene; PHKA2 gene; PHKB gene; PHKG2 gene; preschool child; PYGL gene; PYGM gene; school child; sensitivity and specificity; single nucleotide polymorphism; SLC37A4 gene; Adolescent; Base Sequence; Child; Child, Preschool; Female; Genetic Heterogeneity; Genetic Predisposition to Disease; Glycogen Storage Disease; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Male; Mutation; Open Reading Frames; Reproducibility of Results; Sensitivity and Specificity
|Appears in Collections:||醫學系|
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