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.
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.
Authors: Deeksha S Bali; Jennifer L Goldstein; Keri Fredrickson; Catherine Rehder; Anne Boney; Stephanie Austin; David A Weinstein; Richard Lutz; Avihu Boneh; Priya S Kishnani Journal: Mol Genet Metab Date: 2013-12-19 Impact factor: 4.797
Authors: Irene J Hoogeveen; Rixt M van der Ende; Francjan J van Spronsen; Foekje de Boer; M Rebecca Heiner-Fokkema; Terry G J Derks Journal: JIMD Rep Date: 2015-11-03
Authors: Jing Wang; Hui Yu; Victor Wei Zhang; Xia Tian; Yanming Feng; Guoli Wang; Elizabeth Gorman; Hao Wang; Richard E Lutz; Eric S Schmitt; Sandra Peacock; Lee-Jun Wong Journal: Genet Med Date: 2015-09-24 Impact factor: 8.822