Tag Archives: rare genetic diseases

Speeding Diagnosis of Rare Diseases

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WuXi NextCODE Claritas

Claritas Genomics combines physician experience with next-generation sequencing and WuXi NextCODE’s analytics to accelerate rare disease diagnosis.

It’s one of the most heartbreaking and frustrating things for parents and pediatricians. When a child presents with a constellation of symptoms that doesn’t point to a known disease, what do you do?

Typically, these kids undergo a battery of tests, some of which will eventually be for single genes suspected to play a role in their health problems. But what if those tests come up negative? That leaves the families and doctors wringing their hands as they wonder what to do next.

That was the case with a patient at Boston Children’s Hospital (BCH). He was a boy who, at six months, wasn’t sitting up, smiling, or doing most of the things babies his age typically do. Instead, he seemed “rigid” to his mom, and then he developed a severe respiratory virus and was hospitalized. He also had repeated seizures and eventually needed a tracheotomy—a tube placed through an incision in his throat to help him breath.

Usually, such kids then begin going through what is known as a “diagnostic odyssey”—a long and arduous journey from doctor to doctor and lab to lab.

BCH doctors are trying a new approach. In 2013, the hospital spun out Claritas Genomics, a specialized genetics diagnostics business that combines the experience of the hospital’s physicians with the power of next-generation sequencing and WuXi NextCODE’s advanced analytics. Timothy Yu, a neurologist and researcher at BCH, helped found Claritas to provide a more holistic approach to rare disease.

WuXi NextCODE’s advanced analytics play a key role in improving the speed and efficiency of such diagnostics. Reading the genome isn’t the major challenge anymore—now the issue is finding the relevant mutations in those three billion base pairs.

The data from a single genome can comprise more than 100 gigabytes, which is enough to fill the hard drive on a good laptop computer. Even the exome, which comprises the parts of the genome that encode proteins, can be 15 gigabytes. To diagnose a rare disease, doctors need to find sequence variations and then scour the research to find out what those actually do. That used to take months to years, and many of the variants were simply classified as being of “unknown significance,” without any further information or the ability to check again as the field of knowledge grew.

WuXi NextCODE’s system has begun to make this a click-and-search task. Our knowledgebase can mine all publicly available global reference datasets simultaneously and in real time to show all there is to know about any given variant and its likely biological impact. By keeping the data in a WuXi NextCODE research database, such as the one BCH is growing every day, our system can also quickly rerun the analysis and provide new information as soon as it becomes known.

Claritas is continually expanding the range of its services. Most recently, the group received conditional approval from the New York Department of Health for three new “region of interest assays” as well as one for mitochondrial DNA. That brings the number of Claritas’s approved tests in that state up to six and means more patients in New York will benefit from this new technology.

Children at BCH with ambiguous diagnoses now regularly undergo a whole exome scan early in their clinical journey. The data is then triaged. It is examined first for the most obvious mutations and then more data is progressively analyzed as necessary. With the consent of parents and security measures for privacy, that data can also become part of research datasets at BCH and other major hospitals around the world, so that the growing data pool can benefit that child and others.

This combination of expertise and technology helped Claritas Genomics find an answer for that baby boy and his family mentioned earlier. Heather Olson, the boy’s treating neurologist, had the boy’s exome scanned through Claritas Genomics, and 130 genetic variations were identified that could have caused one or more of the symptoms. WuXi NextCODE’s system helped narrow that down to only six variants that could have possibly been passed on by the boy’s parents. Olson and Yu finally focused on one, a mutation of the BRAT1 gene, which served as a diagnosis. A paper published by Yu, Olson, and colleagues, which describes this mutation and children affected by it, should help other physicians make this diagnosis more quickly in the future.

Yu presented more on Claritas’s novel platform recently at Boston’s Bio-IT World meeting. He explained how the platform helps doctors to much more quickly and accurately diagnose kids with diseases not previously described.

“Thanks to the speed of the platform, we can get a whole clinical exome completed in as little as two weeks,” he said.

The growing database of genetic variants and their effects also means more patients will get an actual diagnosis, rather than walking away still wondering what could be going on.

The ability to diagnose more cases is a start to unravelling the causes of the estimated 7,000 different rare diseases estimated to exist. And it’s a necessary first step towards developing new therapies for those conditions, too.

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Genomics for Rare Diseases: Going Global and Shifting the Care Paradigm

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The use of genomics in rare disease diagnosis and treatment is going global

The benefits of genomics in rare diseases are increasingly making a difference to patients, their families, and their physicians, and they are being scaled globally.

The trend of accelerating the use of genomics in rare disease diagnosis and treatment is going global, driven by the important goal of reaching all people around the world, no matter where they live.

Active programs have now been deployed and exist in many populous countries around the world.

For instance, WuXi NextCODE has established active collaborative efforts in three continents, most recently adding Fudan Children’s Hospital as a partner in its efforts to lead whole genome diagnostics for rare diseases in China.

Over the coming weeks, I expect WuXi NextCODE to continue have news of its dedicated efforts to spread the application of genomics for rare diseases to all geographies.

Diagnosing Rare Diseases: Genomics Shifts the Paradigm

Rare diseases are an area of significant advancement for genomics, as the opportunity for improved diagnosis and treatment through the use of genomics is truly remarkable.

According to the National Institutes of Health (NIH), there are over 7,000 rare diseases affecting between 25 and 30 million Americans, which is nearly 1 in 10 people, making the overall prevalence of rare diseases significant. Since NIH believes that approximately 80 percent of rare diseases have genetic origins, the potential for genomic sequencing, interpretation, and analysis to offer a solution here is truly game-changing.

Every day there are new cases of children with “unknown” diseases, many of which are likely related to a hereditary genetic disorder. Sadly, these children and their families often spend years undergoing testing and experimental treatments for a wide range of diseases in an attempt to properly diagnose and treat them; usually, this so-called “diagnostic odyssey” is accompanied by a very high financial and emotional burden.

Genomics offers the potential to deliver a correct and precise diagnosis for rare diseases that have identifiable genetic causes. Indeed, case studies are rapidly accumulating that show that, by offering genomic sequencing and analysis services to patients with a suspected rare genetic disease, mutations that might be causing the disease may be identified, and thus correct treatment can be employed much earlier to eliminate the burden of a long-term diagnostic and treatment odyssey.  A recent article in Bloomberg BusinessWeek highlighted medical histories of two patients who recently received a diagnosis informed by genomics. In both these representative examples, genomic analyses provided an end to the burden, cost, and stress of their multidecade-long diagnostic odyssey:

  • Jackie Smith, 35, spent the 32 years from age 3 unable to receive a correct diagnosis that could account for her weak limbs and turned-in ankles, despite seeing many doctors on numerous occasions. Indeed, Jackie’s parents were told to “take the 3-year-old girl home and enjoy her while they could” …”[her disease] would probably kill her before she was old enough to drive.”  This past February, using genomic interpretation and analyses from Wuxi NextCODE, Claritas Genomics definitively identified her condition as centronuclear myopathy in less than three weeks.
  • Dustin Bennett, 24, would tremble and violently jerk for hours or days at a time and had been developmentally delayed since childhood. After dozens of doctor visits and incorrect diagnoses—seizures, muscle disorders, mental health problems—a Mayo Clinic genomic-based analysis showed he has episodic ataxia type I, a neurological disease characterized by hours-long attacks with no clear trigger. Dustin, a 24-year-old who functions at a first-grade level, is now on the second round of a medication doctors say should help reduce the frequency and severity of his episodes.

The benefits of genomics in rare diseases – to individuals, their families, and their physicians – are increasingly making a difference to patients.  These benefits are being seen in case after case – and they are being scaled globally, as leading medical centers in many countries around the world are using genomics to support their efforts in diagnosing and treating rare diseases.  I believe passionately in the game-changing potential of genomics to help rare disease patients and I am dedicated to advancing world-leading genomics globally to uncover new solutions for patients.

Population-Scale Research Efforts Enabled by Progress in Sequencing

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population-scale genomics

Significant insights gained from population-scale genomic studies, based on the knowledge of genetic variation and disease causation, will help to enable a new reality of personalized medicine and treatment.

The ability to sequence whole genomes quickly and economically is driving interest in population-scale sequencing efforts that can reveal meaningful insights on a much more systematic basis than previous approaches. A range of large initiatives announced recently are prime examples of the trend in population sequencing, including industry programs by Regeneron and Human Longevity, and the 100,000 Genomes Project by Genomics England. Perhaps better than any other effort since the founding of deCODE in Iceland, the establishment of a high-throughput Genomics Center at Sidra Medical and Research Center in Qatar embodies the movement toward these types of population studies. The eventual goal of the project is to sequence the entire Qatari population of some 300,000 people. But from the beginning, the Sidra facility will help advance genetic mapping projects, including the creation of Arab consensus genome to obtain a better understanding of genetic variants that influence health across Arab populations and, indeed, beyond. In addition to these efforts, the center will focus on uncovering the causes of rare genetic diseases. The significant insights that can be gained from population-scale studies, based on the knowledge of genetic variation and disease causation, will help to enable a new reality of personalized medicine and treatment. And this is where efficient, powerful and industrial-scale analysis will become critical. NextCODE’s analytics and interpretation systems have already been tested at such scale, as they are based on the world’s first and largest population genomics effort—that of deCODE. [see blog post] Our systems will be useful tools to efficiently deliver insights based on the vast amount of data that will be generated by these major population-based efforts to improve the state of global healthcare.

Seeking Genomic Answers to Autism and Rare, Idiopathic Diseases

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rare-diseases-hannes-smarasonAs more is learned about autism spectrum disorders, more questions seem to arise. Yet with DNA sequencing, researchers are able to investigate the genetic roots of this and other diseases that are not yet well understood. It’s another instance in which genomics can shed light upon the workings of that most important organ system—the brain—which is so difficult to analyze.

Institutions around the world have sought to fill in pieces of the autism puzzle with links to other disorders and diagnostic insights, and these efforts have in recent years uncovered a number of possible genetic triggers and pathways. Yet the causes and manifestation of these diseases remain largely elusive.

University College Dublin’s Academic Centre on Rare Diseases (ACoRD) in Ireland, which is world renowned for its discoveries in rare genetics, is using NextCODE’s genome analysis technology to power large-scale, sequencing-based diagnostics programs and genome discovery efforts to study autism and rare pediatric disorders.

Recognizing the enormous potential of large-scale sequencing to mine whole genomes and accelerate discoveries in rare genetic diseases, ACoRD will focus on some of the most challenging areas to inform and provide new directions for research that may help lead to diagnosis, treatment, and even prevention for these disorders. In using NextCODE technology both for analyzing as well as storing large-scale genomic data, ACoRD is well positioned to become a focal point for multinational research and clinical diagnosis in conditions that require the gathering and collective analysis of genomes from many participants in many countries.