Ambry Advances Understanding of Human Disease Through Epilepsy Gene Research


At Ambry, we believe working together is better, that sharing data is essential to finding answers faster. Our scientists embody these beliefs by collaborating with other talented researchers and physicians to understand human disease, most recently in epilepsy genetics. We are proud to have contributed to the clinical research reviewed in the publications “DNM1 Encephalopathy: A New Disease of Vesicle Fission” in Neurology and “Male Patients Affected by Mosaic PCDH19 mutations: Five New Cases” in Neurogenetics.

Ambry scientists, K. Helbig, D. Shinde, and R. Huether collaborated with researchers from numerous esteemed organizations to author “DNM1 Encephalopathy: A New Disease of Vesicle Fission.” This article was featured on the front cover of the July 25th edition of Neurology, a widely read neurology journal.

Their research examined epilepsy-associated mutations in the DNM1 gene, a gene that Ambry previously reported as a candidate gene using our advanced reporting criteria.  Ambry analyzed internally-collected data from whole exome sequencing to discover this gene as a candidate for infantile-onset epilepsy in an extra inquiry process that few labs perform.  Three weeks after Ambry first reported a mutation in this gene in an epilepsy patient, an independent lab published a study in a peer-reviewed scientific journal affirming the DNM1 mutation’s association with epilepsy.

Ambry researchers furthered the field’s understanding of the DNM1 gene through their continued research, which compared various mutations found in epilepsy patients by molecular modeling in the encoded dynamin-1 protein. Their research also sought to characterize the phenotypic spectrum of patients with these mutations. The authors discovered that the spectrum is relatively homogenous, and propose dynamin-1 variants may provide an opportunity for therapeutic intervention.

Ambry scientists H. Newman and K. Helbig contributed to research recently published in Neurogenetics, entitled “Male Patients Affected by Mosaic PCDH19 mutations: Five New Cases.” This research focused on PCDH19, another gene associated with epilepsy. The authors examined five males with mosaic PCDH19 mutations, which can be considered an important addition to the medical and scientific literature, as only four mosaic males had previously been reported.

Typically PCDH19 mutations cause epilepsy and related symptoms only in females, while hemizygous males are asymptomatic carriers. This is hypothesized to be due to a disease mechanism called cellular interference. In this study of five males, their clinical symptoms were similar to those in previously reported females. This similarity demonstrates that mosaic mutations in PCDH19 can have equally profound effects on males as females, and reaffirms the phenotypic similarity of these mutations in all patients.

Both of these research collaborations serve to help us find answers for your patients and your practice. This clinical research underscores the importance of the inclusion of both DNM1 and PCDH19 analysis on epilepsy panels, as Ambry has continually included.

“Male Patients Affected by Mosaic PCDH19 mutations: Five New Cases” reaffirms the importance of testing males with epileptic encephalopathy for PCDH19 mutations.  The cases presented in this research show that the effect of PCDH19 mutations is not solely limited to female patients, while providing an indication of the symptoms that older male patients might progress toward. In addition, the phenotypic similarity of the patients with PCDH19 mutations provides clinicians with valuable insight on treatment for affected men.

“DNM1 Encephalopathy: A New Disease of Vesicle Fission” demonstrates the importance of the inclusion of DNM1 on epilepsy panels, as knowledge of a specific mutation in a patient could steer future treatment decisions. The results provide context for specific epilepsy phenotypes, as DNM1 is associated with relatively homogenous phenotypic symptoms. The association between gene mutations and phenotypes examined in this research are helpful for prognostication and therapeutic development.

Ambry includes both DNM1 and PCDH19 on our broad epilepsy panels, as well as more specific tests. View our epilepsy test menu here.

Read “DNM1 Encephalopathy: A New Disease of Vesicle Fission” here.

Read “Male Patients Affected by Mosaic PCDH19 mutations: Five New Cases” here.


Find Answers & Improve Patient Care

Ambry is committed to delivering the most accurate genetic test results possible. Learn more about our products today.

Love this article?

Get stories just like it, delivered right to your inbox.



The information, including but not limited to, text, graphics, images and other material contained on this blog are for informational purposes only. The purpose of this blog is to promote broad understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this blog. Ambry Genetics Corporation does not recommend or endorse any specific tests, physicians, products, procedures, opinions or other information that may be mentioned on this blog. Reliance on any information appearing on this blog is solely at your own risk.