Quest Diagnostics has launched a next-generation sequencing-based panel to diagnose Charcot-Marie-Tooth disease, as well as a handful of Sanger-based tests for other rare neurological disorders, which were developed through its Athena Diagnostics business.
The Charcot-Marie-Tooth panel includes 23 genes associated with the disorder, including the full exons of each gene and splice sites. Average coverage is 100-fold and turnaround time is three to four weeks.
The firm has not yet determined a price or its reimbursement strategy for the test, and declined to disclose what sequencing platform it was running on.
The Sanger-based tests, which screen between one and eight genes, are for a number of rare neurological disorders, including myofibrillar myopathy, hereditary sensory and autonomic neuropathy, hereditary neuralgic amyotrophy, hypokalemic periodic paralysis, limb girdle muscular dystrophy, benign familiar infantile epilepsy, and familial paroxysmal kinesigenic dyskinesia.
Physicians who want to order the NGS-based Charcot-Marie-Tooth panel will also have the ability to customize their order.
Aside from the full 23-gene panel, physicians can order smaller number of genes that would be relevant for the patient's specific phenotype.
"If you want to order a next-gen panel, you should really consider doing a phenotypic evaluation," Joseph Higgins, medical director at Athena Diagnostics, told Clinical Sequencing News. "You may only order 10 [genes]. Or if you're in a certain category where it's recessive, you may only order about three or four."
Additionally, all patients will first be screened for deletions and duplications to the PMP22 gene using multiplex ligation-dependent probe amplification.
Deletions and duplications to PMP22 are "one of the highest indicators at getting this condition," explained Steve Becker, executive director of Quest's neurology segment solutions.
"Our approach is to first do a dup/del using MLPA technology," said Becker. "If we don't get a positive, we'll follow into gene sequencing."
Quest previously offered a Sanger-based test for Charcot-Marie-Tooth, said Higgins. He noted that the company essentially has a built-in validation for the NGS-based test because it has built up a huge database of known variants from the Sanger version.
"Our next-gen panel has been validated against known mutations that have been confirmed with Sanger sequencing," said Higgins. In those validation studies, the panel was 100 percent concordant with mutations identified by Sanger sequencing.
Unknown mutations that are picked up by the next-gen panel will be confirmed with Sanger sequencing, but known mutations will not.
Quest has its own bioinformatics pipeline, Athena Insight, which it will use for analysis and interpretation of the test. The pipeline will help determine the relevance of unknown mutations by assigning each of them a "pathogenicity score," Higgins added.
The Charcot-Marie-Tooth test is not Quest's first foray into next-gen sequencing. Last fall, it published a validation study of its laboratory-developed HIV tropism test that is based on a combination of Sanger sequencing and next-generation sequencing on Roche's 454 GS Junior platform (CSN 10/10/2012).
Additionally, Andrew Grupe, the senior director of pharmacogenomics in Quest's Celera business, previously told CSN that the company is evaluating all of the desktop sequencing instruments, including the Illumina MiSeq, Life Technologies' Ion Torrent PGM, and Roche's 454 GS Junior, as part of a larger effort to develop NGS-based tests (CSN 7/11/2012).
Becker said that the company is working on developing additional tests based on next-gen sequencing, but did not disclose for what conditions. Additionally, he said that the Sanger-based neurology tests will remain as Sanger sequencing tests for now because they screen for such a small number of genes.