Collaborative Study of Whole Exome Sequencing Offers New Hope for Children with White Matter Disorders

SAN DIEGO–(BUSINESS WIRE)–Illumina, Inc. (NASDAQ: ILMN), Children’s National Health System and The
University of Queensland (UQ) announced today that a study using whole
exome sequencing (WES), a method to look at all the genes in the genome
at once, yielded clinical diagnoses for 42 percent of patients with
white matter abnormalities that had been unresolved an average of eight
years.
White matter disorders are progressive and involve age-related weakness
in the part of the nerves that connect various parts of the brain to
each other and to the spinal cord. This group of disorders are found in
1 per 7,000 children born each year. The study brought together 28 named
collaborators, led by Children’s National and included researchers from
Illumina and The University of Queensland.
The results of the study, entitled “Whole exome sequencing in patients
with white matter abnormalities,” are available online in the Annals
of Neurology and the full article can be accessed here.
The paper will also be published in the June print edition (Volume 79,
Issue 6).
“The term ‘rare’ genetic disease is something of a misnomer, since up to
350 million people across the world can be impacted by these disorders,”
said Adeline Vanderver, M.D., Director of the Myelin Disorders Program
at Children’s National and lead author on the study. “Our study found
that next generation sequencing could shine a diagnostic light on an
especially challenging group of genetic disorders that impact the
brain’s white matter.”
“We were delighted by the power of this approach,” adds co-author Ryan
J. Taft, Ph.D., Director of Scientific Research at Illumina. “In this
study, use of next-generation sequencing-based WES dramatically
increased the diagnostic yield and reduced the time to diagnosis.”
“White matter disorders can have a devastating impact on patients and
their families,” said study co-author Cas Simons, Ph.D., from the
Institute for Molecular Bioscience Centre for Rare Diseases Research at
UQ. “Access to a timely and accurate diagnosis is critical to inform
many health care decisions and improve quality of life for patients.”
More than 100 genetic disorders are linked to white matter abnormalities
in the central nervous system. At least 10 different chemicals make up
the myelin, a fatty insulation layer, and the myelin sheath plays a
critical role in smooth transmission of electrical impulses along nerve
cells. A cluster of rare genetic disorders known as the
leukodystrophies, which cause progressive degeneration of the brain’s
white matter, are tied to genetic flaws in how myelin makes or uses its
essential mix of chemicals.
Standard approaches to diagnose white matter disorders fail in nearly 50
percent of these children, complicating their care and exacting a
substantial psychological toll on families, Dr. Taft says. The human
genome contains roughly 3 billion letters of DNA. The exome, the
protein-coding region of the genome, represents just 2 percent of this
genetic code but contains most of the variants known to be related to
disease.
MRI (magnetic resonance imaging) has been tapped for the last 20 years
to recognize telltale patterns of leukodystrophies, yet nearly half of
patients lack concrete diagnoses. Because WES ferreted out diagnoses for
other stubbornly unsolved genetic disorders, the research team has
proposed that the technique could answer genetic cold cases thought to
be leukodystrophies.
The research team identified 191 families with unresolved cases of
leukoencephalopathy thought to be genetic in nature. Of this group, they
diagnosed 101 families using MRI pattern recognition followed by
standard biochemical and genetic testing. For the 90 cases that remained
undiagnosed, 71 family groups of at least three people were included in
the study and provided the high-quality samples needed for WES analyses
by the research team. While patients ranged from 3 to 26 years old at
the time of sequencing, for some, symptoms began at birth. This research
was performed utilizing Illumina technology.
According to the study, adding WES to the diagnostic tools already at
clinicians’ disposal “may decrease the number of patients with unsolved
genetic white matter disorders from 50 percent to less than 30 percent.
Taking into consideration the clinical and psychosocial costs of
prolonged diagnostic odysseys in these families, this is substantial.”
The diagnoses led to additional precision in some patients’ clinical
care, with families with certain mutations being referred to specialized
clinics to undergo monitoring for cancer. Based on these results the
team is now investigating the use of whole genome sequencing, which
could further increase the diagnostic yield, in a multi-site prospective study
of children with neurodevelopment disorders.
About Children’s National Health System
Children’s National Health System, based in Washington, DC, has been
serving the nation’s children since 1870. Children’s National is a
Leapfrog Group Top Hospital, Magnet® designated, and was ranked among
the top 10 pediatric hospitals by U.S. News & World Report 2015-16.
Home to the Children’s Research Institute and the Sheikh Zayed Institute
for Pediatric Surgical Innovation, Children’s National is one of the
nation’s top NIH-funded pediatric institutions. With a community-based
pediatric network, seven regional outpatient centers, an ambulatory
surgery center, two emergency rooms, an acute care hospital, and
collaborations throughout the region, Children’s National is recognized
for its expertise and innovation in pediatric care and as an advocate
for all children. For more information, visit ChildrensNational.org,
or follow us on Facebook
and Twitter.
About Institute for Molecular Bioscience, The University of
Queensland (UQ)
The University of Queensland’s Institute for Molecular Bioscience (IMB)
is one of Asia-Pacific’s leading life sciences research institutes.
Established in 2000, IMB is committed to improving quality of life
through research. IMB researchers work in partnership with academic,
industry and clinical colleagues around the world to advance knowledge
in areas including rare diseases, pain, inflammation and superbug
infection. The institute has a focus on translating its new knowledge
into drugs, diagnostics and technologies to more effectively prevent,
detect and treat disease; and pursue opportunities in a range of
biotechnology applications for health, industry and the environment.
About Illumina
Illumina is improving human health by unlocking the power of the genome.
Our focus on innovation has established us as the global leader in DNA
sequencing and array-based technologies, serving customers in the
research, clinical and applied markets. Our products are used for
applications in the life sciences, oncology, reproductive health,
agriculture and other emerging segments. To learn more, visit www.illumina.com and
follow @illumina.
Forward-Looking Statements
This release may contain forward-looking statements that involve risks
and uncertainties. Important factors that could cause actual results to
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including our most recent filings on Forms 10-K and 10-Q, or in
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