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ALISO VIEJO, Calif.–(BUSINESS WIRE)–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 …

ALISO VIEJO, Calif.–(BUSINESS WIRE)–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 the 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.
References

  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 privately-held healthcare company with the most
comprehensive suite of genetic testing solutions for inherited and
non-inherited diseases. Since 1999, Ambry has tested approximately
nearly one million patient samples benefiting >94% of all U.S. patients
covered by public and private insurers. Ambry is dedicated to scientific
collaboration by offering its rapidly growing database of anonymized
genomic data (variant frequencies) free to the global medical research
community to fulfill the promise of the human genome to cure or manage
all human disease. Ambry is dedicated to the belief that human health
should not be patented or owned, and genomic data should be freely
shared so we can try to understand all human disease. For more
information about Ambry Genetics, visit ambrygen.com.

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