Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin
2012; Elsevier BV; Volume: 15; Issue: 2 Linguagem: Inglês
10.1038/gim.2012.104
ISSN1530-0366
AutoresJing Wang, Hong Cui, Ni‐Chung Lee, Wuh‐Liang Hwu, Yin‐Hsiu Chien, William J. Craigen, Lee‐Jun C. Wong, Victor Wei Zhang,
Tópico(s)Neurogenetic and Muscular Disorders Research
ResumoAbstract 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. Genet Med 2013:15(2):106–114
Referência(s)