This article has been updated with additional information from Athena Diagnostics.
NEW YORK (GenomeWeb) – Athena Diagnostics has launched a whole-exome sequencing service for the diagnosis of rare neurological disorders that was developed by Personalis.
The test, called Neurome, is available from Athena, Quest Diagnostics' genetic testing business for neurological disorders, and is performed in Personalis' CLIA-certified and CAP-accredited laboratory in Menlo Park, Calif. Personalis, which also performs the test interpretation, developed the test exclusively for Athena.
Neurome is designed to find the genetic basis of ill-defined and unexplained neurological disorders with a suspected genetic cause, such as some forms of developmental delay, epilepsy, hearing loss, and muscular dystrophies. It focuses primarily on pediatric patients, where neurological disorders are often difficult to diagnose with other tests.
A Quest spokesperson told GenomeWeb that the company evaluated several options for partnering on an exome test and decided to go with Personalis because it "has produced strong evidence demonstrating the robustness and clinical value of its services."
The diagnostic yield of the test is not yet available and will depend in part on what types of prior testing patients have had, but it "should exceed current exome tests because of its technical and clinical focus on neurological conditions," said Joseph Higgins, medical director of neurology at Quest, in a statement.
The test will complement Athena's more targeted panel testing for epilepsy and other conditions, according to the spokesperson. A year ago, for example, Athena launched a number of NGS-based epilepsy panels that cover up to 141 disease genes.
Personalis CEO John West said that Athena, which was acquired by Quest from Thermo Fisher Scientific in 2011, has been selling genetic tests directly to neurologists for decades and is well known in this market.
Neurological disorders, he said, are a "pretty important segment of the market and an area where an exome can add a lot." While for many other disease areas, such as cardiology, non-genetic diagnostic tools are available, not many informative tools exist in neurology, he said, "so there is big demand for genetics to help interpret these cases."
Following guidelines from the American College of Medical Genetics and Genomics, Athena recommends the Neurome test as a first-line test only if no targeted testing is available. Generally, the test is recommended for patients with a neurological disease of unknown cause with suspected genetic origin and for patients with a highly heterogeneous neurological disorder where targeted testing failed to deliver a diagnosis.
The price of the test is $4,750 for a single proband and $8,500 for a family trio. Athena said it will bill institutions or patients directly and not deal with reimbursement. According to its website, the turnaround time for Neurome is 10 to 15 weeks.
Neurome is currently not available in New York, where Personalis' clinical laboratory is not licensed yet, as well as in eight other states, including California, Florida, and Pennsylvania. According to Personalis CEO John West, those latter states are not included because they have so-called anti-markup legislation that limits the amount physicians or other suppliers of diagnostic tests can bill for tests or services they purchase from other suppliers. West said Athena might be able to offer the test in at least some of these "anti-markup states" in the future because the rule appears to be restricted to pathology services in those states.
The Neurome test is based on Personalis' ACE Exome technology, which augments coverage for more than 8,000 disease-related genes, provides near-complete coverage for more than 6,000 clinically relevant genes, and includes clinically interpretable non-exonic regions.
Personalis itself has been offering its ACE Clinical Exome test for the diagnosis of rare Mendelian disorders, including neurological disorders. Last fall, the company launched an update for the test, for which it charges $7,500 per case.
The main technical difference between Neurome and the ACE Clinical Exome test, West explained, is that Neurome does not include structural variant detection from low-coverage sequence data. Most patients receiving Neurome will likely already have undergone microarray-based testing for copy number variants, so there was no need to include this capability in Neurome.
On the interpretation side, Neurome uses a phenotype-driven approach that ranks variants based on clinical features. It focuses on genes previously associated with neurological disorders first, though the analysis can be broadened to other genes. The test also allows for re-analysis in the future when additional disease-associated variants have been discovered. "We're not restricted by the content that's understood today," West said.
All variants to be reported are confirmed by Sanger sequencing or other orthogonal methods. The report, which is prepared by Personalis' clinical team and distributed to the ordering physician by Athena, does not contain secondary or incidental findings "to avoid complication not related to the actual neurologic condition," West said.
ACMG recommends reporting secondary findings in 56 genes, both for pediatric and adult patients, but the issue of reporting variants for adult-onset diseases in children has been controversial.
Athena's launch of the Neurome test comes at a time when other laboratories have also started to offer disease-specific exome tests and moved to exomes with enhanced coverage of certain areas.
Claritas Genomics, for example, released its ClariView Exome for Pediatric Neurology last summer. The test, which sequences the exome on both the Ion Proton and the Illumina MiSeq platforms, analyzes 614 disease genes.
Also, Baylor College of Medicine launched an exome test with enhanced coverage of 3,600 genes last fall and Emory Genetics Laboratory introduced a clinical exome with added coverage for 4,600 genes last year, developed with the Children's Hospital of Philadelphia and Partners HealthCare's Laboratory of Molecular Medicine.
West said that competitors' clinical exomes usually add more probes to the capture and do not go outside the exome, whereas Personalis performs a separate capture step and includes non-coding regions.