see Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin
For metabolic disorders with similar symptoms and multiple potential genetic origins, definitive diagnosis has relied on sequencing individual candidate genes. Whole-exome sequencing preÂsents an attractive alternative, as demonstrated in a proof-of-concept report by a collaborative group at Baylor College of Medicine and National Taiwan University Hospital. The panel test included 16 genes known to cause either liver or muscle forms of glycogen storage disease (GSD). Obtaining definitive results for 17 patients with clinical, histochemical, and/or enzymatic evidence of a GSD but negative or inconclusive molecular findings, took about eight weeks, including confirmatory Sanger sequencing. The test correctly identified all types of genetic alterations, from single-nucleotide substitutions to large deletions involving more than one exon. By contrast, the current conventional approach is more expensive and much more time-consuming, leaving families in limbo and delaying potentially lifesaving treatment. The authors point out that the technique is well suited for clinical diagnostics and can be scaled up and automated with robotic liquid handling. The technique is likely to be employed in situations such as this example, in which genetically heterogeneous biochemical disorders can be sorted out, but its use in many other clinical contexts will certainly grow. —Karyn Hede, News Editor
