Investigation into the effectiveness of an extended gene panel for the diagnosis of complex neurometabolic phenotypes

BRC-supported Dr Philippa Mills, Professor Peter Clayton and Professor Paul Gissen have led an investigation into the effectiveness of a gene panel, targeting 614 genes, in establishing a diagnosis for patients presenting with a wide array of neurometabolic phenotypes.

The study looked at the effectiveness of an Inborn Errors of Metabolism gene panel at establishing a diagnosis in patients presenting with a range of neurological features, all of whom had undergone extensive previous investigations but lacked a definitive molecular diagnosis. The panel was shown to be a powerful tool which improved diagnostic ability in the clinical setting.

Despite the large number of genes included, coverage of targeted areas was similar or indeed superior to that for other gene panels. Genetic defects that could, at least partially, explain the observed phenotype could be identified in 53% of patients and when biochemical abnormalities were present this rose to 89%. 

The findings suggest that gene panel approaches provide a cost-effective method for testing patients with neurometabolic disorders, enabling a more timely diagnosis, and therefore more prompt treatment inititation.

Currently, patients with suspected neurometabolic disease can undergo extensive and often invasive diagnostic testing. Delays or difficulties establishing a definitive diagnosis are commonly encountered during this process.

Extended gene panels have gained popularity for the diagnosis of genetically heterogeneous conditions providing a rapid method for identifying mutations in genes. This would be of particular benefit for neurometabolic disorders, as early diagnosis is crucial due to early initiation of treatment resulting in more positive outcomes.

The findings of this study have been published in Brain