Ambry Genetics and Collaborators Publish Vital Processes and Data to Better Understand New Gene Associated with Unexplained Neurodevelopmental Disorder


Ambry Genetics
15 Argonaut
Aliso Viejo, CA 92656

Aliso Viejo, CA – September 6, 2016 – Ambry Genetics (“Ambry”) announces two publications that help uncover how a newly characterized gene found by diagnostic exome sequencing (DES), SON, plays a role in intellectual disability (ID) and developmental delay (DD). One study, published in Genetics in Medicine (GIM), is the first to publish fully-vetted scoring criteria for clinical reporting of novel candidate gene findings found by WES. The next study, published in American Journal of Human Genetics (AJHG), demonstrates the use of these criteria to identify a new ID syndrome associated with specific mutations in the SON gene. These studies emphasize how systematic processes to report genetic findings found via DES and laboratory-clinician collaborations involving families can help understand complex processes in human development, forging new pathways to treatments for patients.

Rare diseases affect 25-30 million people in the U.S., 75% of whom are children, and 25% of pediatric inpatient admission are due to these diseases.1,2 Thus far, the responsible gene has been discovered for only half of 6,000-7,000 rare diseases with suspected genetic causes.3

DES is now a commonly ordered test for individuals with undiagnosed genetic disorders. In addition to providing a diagnosis for characterized diseases, DES has the capacity to uncover novel candidate genes for disease. Identifying an underlying genetic cause is one of the most important steps toward timely and effective interventions for patients. DES is a source of discovery for new disease-causing genes, with a rapid pace for these discoveries projected in future. 

Ambry was the first to offer clinical DES on a commercial basis in 2011. Leveraging this wealth of experience and data, Ambry authors were the first to publish transparent, vetted systematic criteria for the clinical reporting of candidate genes identified by DES in the GIM publication. These help to assess and classify the clinical meaning of genetic variants of uncertain significance, which can ultimately provide healthcare providers and patients with a clearer result and help identify treatments.

Deepali Shinde, PhD, Clinical Genomics Scientist at Ambry and study author, said, “Analyzing candidate gene-disease associations is challenging due to the lack of previously reported patients. Until genetic data from patients are available to characterize a newly discovered gene-disease association, Ambry’s highly trained scientists analyze information about the function and expression of candidate genes garnered from peer-reviewed literature and genetics conferences. We are dedicated to translating all of this into a diagnostic report to explain a patient’s clinical symptoms in an understandable and meaningful manner.”     

Numerous genes have been implicated in ID and DD disorders, making this an extremely complex group of disorders to understand. Using the novel candidate gene scoring criteria mentioned above, Ambry’s exome sequencing team issued the first clinical report proposing a de novo heterozygous loss-of-function mutation in the SON gene to cause an ID syndrome in 2014. Subsequent patient recruiting through data sharing and results from functional studies by research collaborators at University of South Alabama Mitchell Cancer Institute ascertained the causal role of SON in the AJHG publication. 20 patients with mild to severe ID and/or DD were all found to have de novo loss-of-function (LoF) mutations in SON. Studied patients had a wide clinical spectrum, with all having ID and distinctive facial features. Many also had brain malformations, neurological features and musculoskeletal abnormalities. This international study discovered a new disease gene underlying a unique neurodevelopmental syndrome and delineated the clinical spectrum due to SON haploinsufficiency. 

Erin Ahn, PhD, lead author from University of South Alabama Mitchell Cancer Institute, said, “It has been truly amazing working on this with scientists and clinicians internationally, particularly at Ambry Genetics and at Radboud University. Translating the knowledge gained from molecular biology research in my laboratory on SON towards understanding the mutational mechanism of this gene in patients’ cells has given me an appreciation for the importance of collaboration between physicians, research and clinical laboratories in increasing diagnostic rates for improved patient care.”

Both studies were successful due to a significant amount of cooperation between laboratories, healthcare providers and patients. Many disease genes are rare, but making families “partners in the discovery efforts”4 can provide patients, families and clinicians the opportunity to connect and help through similar studies.  These types of studies are important in paving the way for future diagnoses, treatments and preventive care.

Ambry engages in ongoing research, both internally and with collaborators. For a listing of peer-reviewed research publications, please visit here.


  1. Costa T, et al. The effect of Mendelian disease on human health: a measurement. Am J Med Genet. 1985;21:231-42. 
  2. Dodge JA, et al. The importance of rare diseases: from the gene to society. Arch Dis Child. 2011;96:791-2. 
  3. Boycott KM, et al. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet. 2013;14:681-91. 
  4. Might M and Wilsey M. The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated. Genet Med. 2014;16:736-7.

About Ambry Genetics ®

Ambry Genetics is a leader in clinical diagnostic and software solutions, combining both to offer the most comprehensive genetic testing menu in the industry. Ambry is both College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified. As part of the Konica Minolta family, Ambry is responsibly applying new technologies to the clinical molecular diagnostics market to bring about precision medicine. For more information about Ambry Genetics, visit

Press Contact:
Dina Scaglione
Director, Marketing
949 457 4355

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