Who Should Undergo Screening?
Given that some patients had the C9ORF72 mutation even without a strong family history, "the most important immediate clinical implication is that we will likely begin screening patients for this mutation once a standard laboratory test for this gene becomes available," Dr. Dickerson said.
In a commentary, Rosa Rademakers, Ph.D., of the Mayo Clinic in Jacksonville, Fla., argued that the use of a clinical screening algorithm to decide whether to test for the C9ORF72 mutation in a patient with a family history of ALS or FTD – or when a patient is behaviorally impaired – may not work, because detailed information about family history is often unavailable. Instead, it should be considered in all patients, particularly because 6%-7% of whites with sporadic disease in the Lancet Neurology paper had the mutation, and the clinical phenotype associated with the C9ORF72 expansion extends beyond FTD and ALS. At the moment, however, caution is advised on testing because "our present understanding of the disease penetrance and range of clinical phenotypes associated with this mutation is poor and the smallest repeat size needed for pathogenicity is unknown," Dr. Rademakers wrote.
The sources interviewed for this article did not have any relevant financial disclosures. Dr. Rademakers disclosed that she has a patent pending on the discovery of the hexanucleotide repeat expansion in the C9ORF72 gene.