Ambry debuts genetic test for AADC deficiency, other rare disorders
Whole genome sequencing, RNA analysis aimed at speeding diagnosis
Ambry Genetics announced a new genetic test designed to speed the diagnosis of rare genetic conditions such as aromatic l-amino acid decarboxylase (AADC) deficiency.
The company said the test, called ExomeReveal, combines whole exome sequencing (WES) with Ambry’s RNA analysis technology to shorten a patient’s diagnostic journey and improve care.
“As the first company to pioneer commercial exome testing in 2011 to today, Ambry Genetics has always been on the forefront of applying the latest scientific evidence to the identification of genetic causes of rare diseases,” Tom Schoenherr, CEO at Ambry, said in a company press release. “The ExomeReveal test is the most recent example of our company’s commitment to innovation, and our investment in providing patients with the most comprehensive clinical genomics tests available.”
AADC deficiency is a rare genetic disorder caused by mutations in the DDC gene. These genetic alterations lead to a deficiency in essential neurotransmitters in the brain. Establishing a definitive diagnosis requires genetic testing to identify the presence of disease-causing mutations in the gene.
WES is a technique that analyzes all DNA sequences of the exome, the portion of human genome that provides instructions for making proteins. Unlike tests that look at DNA alone, the ExomeReveal also analyzes RNA, the intermediate molecule generated from DNA that serves as a template for protein production.
Splicing genes
RNA molecules undergo a process called splicing, in which non-coding sequences called introns are removed from the primary RNA transcript. This process generates a functional, protein-coding sequence consisting only of exons, called messenger RNA (mRNA).
Mutations in protein-coding genes may lead to aberrant splicing of mRNAs, resulting in altered protein production. Studying these splicing variants can provide valuable insights into the functional consequences of genetic mutations, particularly those with unknown or less characterized impacts.
“Every diagnosis matters to patients and families experiencing the rare disease diagnostic odyssey,” said Elizabeth Chao, MD, chief medical officer at Ambry. “By adding RNA analysis capabilities to our exome sequencing test, we will be able to identify the cause of rare disease in more patients, enabling better medical care and the potential for new treatment options.”
Ambry has validated the ExomeReveal test protocol via an early access program. From the samples profiled by WES and based on the initial results, about 5% were referred for RNA analysis. A clinically meaningful result was found in about one in 50 patients.
According to the company website, RNA analysis increases the diagnostic yield by 2% to 3%, meaning fewer cases are likely to go unnoticed.
Patients undergoing the ExomeReveal test are automatically enrolled at no cost in the company’s Patient for Life program, in which Ambry continuously re-analyzes patients’ data for updates to exome reports as new scientific discoveries are made. Patients are informed if their status changes, and can discuss their results with a genetic counselor.
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