Posts (19)

4 days ago · Precision genomics may offer clues to unexplained low blood cell counts

By Jay Furst

Mrinal Patnaik, M.B.B.S.

Precision genomics has opened the door to identifying the drivers for cancer and other diseases. Its value as a diagnostic tool isn’t limited to the underlying disease biology, however. It also can help diagnose and determine targeted therapies for patients with unexplained illnesses.

Mrinal Patnaik, M.B.B.S., a Mayo Clinic hematologist, and colleagues conducted research with patients who had unexplained low blood cell counts, or cytopenias, and found that a precision genomics approach has the potential to change clinical treatments and enable personalized care. Dr. Patnaik is associate professor of medicine and assistant professor of oncology, Mayo Clinic College of Medicine and Science.

“Adult patients with unexplained cytopenias need appropriate testing before subjecting them to trial-and-error therapies,” says Dr. Patnaik, corresponding author of the study, published in Mayo Clinic Proceedings. “A significant proportion of these patients could have genetically defined inherited bone marrow failure syndromes, which need specialized treatment. Precision medicine testing has the potential to alter their clinical management.”

Researchers evaluated 68 patients with unexplained cytopenias. About one-third of patients were found to have inherited bone marrow failure syndromes, while 44% did not fit under a known clinical syndrome, diagnosed as clonal or idiopathic cytopenias of undetermined significance. The remaining patients didn’t fit either category.

“Adult patients with unexplained cytopenias need appropriate testing before subjecting them to trial-and-error therapies. A significant proportion of these patients could have genetically defined inherited bone marrow failure syndromes, which need specialized treatment. Precision medicine testing has the potential to alter their clinical management.”

Mrinal Patnaik, M.B.B.S.

Dr. Patnaik and colleagues then conducted a chart review to determine how the information was applied later in the clinical setting. In 25% of the cases, doctors and patients made changes in clinical management, including decisions regarding therapeutic interventions, donor choice and conditional regimens for stem cell transplantation.

Even when a definite diagnosis couldn’t be reached, patients received a tailored follow-up plan that was informed by the genomic work.

“Clearly the information was of value and led to changes in treatment,” says Dr. Patnaik, who has a special research interest in blood cancers called myelodysplastic and myeloproliferative neoplasms. “Our data suggests that it is possible to use this testing in routing clinical practice, and the results should encourage clinicians to consider these tests.”

The study was funded in part by the Center for Individualized Medicine’s Gerstner Family Career Development Award and a grant from the National Center for Advancing Translational Science, which is part of the National Institutes of Health.

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Mon, Oct 21 7:00am · What men need to know about breast cancer risk

Male breast cancer is a rare disease, comprising 1% of all breast cancers, but the number of men diagnosed is on the rise.

“And there is an increasing appreciation of differences in the tumor biology of female breast cancer versus male breast cancer,” says Siddhartha Yadav, M.D., co-author of a Mayo Clinic study published in the journal Cancer.

“In this study, we looked at how male breast cancer has been treated in the 21st century, as there is limited understanding of treatment patterns and prognostic factors,” Dr. Yadav explains. “There is a need for studies focused on this unique population.”

According to Dr. Yadav, in many ways, male breast cancer resembles female breast cancer, but there are important differences:

  • Male breast cancer tends to present at an older age, with more frequent lymph node metastases and a higher percentage of estrogen receptor–positive (ER+) tumors compared with female breast cancer.
  • Inherited risk factors for male breast cancer also are slightly different. In contrast to female breast cancer, male breast cancer is more likely to occur within the setting of a BRCA2 mutation rather than BRCA1 mutation.
  • In addition, lower levels of male sex hormones, particularly testosterone) is a known risk factor for male breast cancer

In the last 20 years, there has been significant progress in the local and systemic management of female breast cancer, but it is unclear whether these advances have been applied to the management of male breast cancer.

“In this study, we looked at how male breast cancer has been treated in the 21st century, as there is limited understanding of treatment patterns and prognostic factors. There is a need for studies focused on this unique population.”

Siddhartha Yadav, M.D.

Researchers identified several factors associated with better overall survival in male breast cancer including, residing in a higher income area, having progesterone receptor–positive tumors, and receiving chemotherapy, radiotherapy, and endocrine therapy. In addition, they demonstrated that the treatment of male breast cancer has evolved over the past decade, with increases in the rates of total mastectomy, radiotherapy after breast conserving surgery, ordering of Oncotype DX testing to estimate the likelihood of disease recurrence, and the use of hormonal therapy.

“The results of the current study highlight unique practice patterns and factors associated with prognosis in patients with male breast cancer, furthering understanding of the treatment and prognosis of male breast cancer and identifying unanswered questions for future research,” says Dr. Yadav.

What men need to know about hereditary breast cancer risk

Genetic testing can play an important role in the care of men with breast cancer. A recent study suggested that up to 18% of men with breast cancer have an inherited gene mutation. The National Comprehensive Cancer Network recommends offering genetic testing to all men with a personal history of breast cancer.

Inherited or hereditary cancer risk is caused by a gene mutation that is passed down from parents to children. A mutation is a change in a gene that causes the gene to not work correctly. Two genes commonly linked with an increased risk for male breast cancer are BRCA1 and BRCA2. Different cancers, affecting both men and women, are also linked to mutations in these genes, including breast, ovarian, and prostate cancer. These mutations may be passed down to children. Other family members, including parents, siblings, and more distant relatives may also be at risk.

“If a man has a family or personal history of male breast cancer, a family history of breast or ovarian cancer, especially at younger ages, is of Ashkenazi or Jewish descent, or has a known family history of BRCA1 or BRCA 2 mutation, we would encourage him to talk to a provider or a genetic counselor to see if genetic testing is right for him,” says Sarah Kroc, a Mayo Clinic genetic counselor, in the Department of Clinical Genomics.

“As more high-risk men undergo genetic testing, more will be learned about inherited cancers in men. Knowing this information may help improve decision making about cancer prevention, detection and treatment options, both for patients and their families.”

Sarah Kroc

Kroc acknowledges that estimating a person’s cancer risk is complex.

“As more high-risk men undergo genetic testing, more will be learned about inherited cancers in men,” says Kroc. “Knowing this information may help improve decision making about cancer prevention, detection and treatment options, both for patients and their families.”

Learn more about BRCA mutations and hereditary cancers in men at: Mayoclinic.org and National Cancer Institute – cancer.gov.

Inherited genetic mutations can play a major role in some cancers. Watch this Video Q&A About Cancer & Genomics  featuring Jewel Samadder, M.D., oncology nurse Kelli Fee-Schroeder and genetic counselor Maggie Klint from Mayo Clinic.

Watch this Mayo Clinic Minute on male breast cancer.

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Tue, Oct 15 12:35pm · Mayo researcher secures NIH grant to advance care of rare disease

Eva Morava-Kozicz, M.D., Ph.D. received a $5 million grant from the National Institutes of Health to study frontiers in congenital disorders of glycosylation (CDG). These disorders often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants.

“This grant will allow us to leverage cross-disciplinary, team-based clinical science to address decades of unresolved questions, increase clinical trial readiness, advance and share knowledge, develop treatment, and meet unmet patient needs,” says Dr. Morava-Kozicz.

Dr. Morava-Kozicz conducts translational research in congenital disorders of glycosylation and mitochondrial disorders and is actively involved in developing dietary therapies in genetic disorders. In addition to her roles as a pediatrician, geneticist and metabolic specialist, she has decades of experience in the diagnostics, follow-up and treatment in inborn errors of metabolism, especially congenital disorders of glycosylation and in mitochondrial disorders.

As principal investigator of the multicenter study on the natural history of congenital disorders of glycosylation, Dr. Morava-Kozicz knows first-hand what gaps need to be addressed.

In response to this need Dr. Morava-Kozicz established a nation-wide network of 10 regional centers to:  

  • Define the natural history, validate patient reported outcomes and share CDG knowledge
  • Develop and validate new biochemical diagnostic techniques and therapeutic biomarkers to increase clinical trial readiness
  • Evaluate whether dietary treatments restore appropriate glycosylation to improve clinical symptoms and quality of life

The grant supports the new Frontiers in Congenital Disorders of Glycosylation consortia, through the Rare Diseases Clinical Research Network (RDCRN), aimed at fostering collaborative research among scientists to better understand how rare diseases progress and to develop improved approaches for diagnosis and treatment.

Congenital disorders of glycosylation are a group of over 150 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. They typically present as multi-systemic disorders with a broad clinical spectrum including, but not limited to, developmental delay, an abnormally low level of muscle tone, abnormal magnetic resonance imaging findings, skin manifestations, and hemorrhaging or clotting disorders. Neurological abnormalities may also be present. There is considerable variation in the severity of this group of diseases ranging from a mild presentation in adults to severe multi-organ dysfunctions causing infantile death.

An important focus of the award is on clinical trial readiness. In order to be prepared to conduct clinical trials the consortia needs to have strong natural history studies that show how the disease progresses. This will lead to ways to measure outcomes of treatments and biomarker studies that provide indicators of how a drug is working in patients.

Collaboration is key. The consortium includes numerous partner research teams from different sites, along with rare disease patients and advocacy groups as research partners. Scientists from different institutions will come together to share patients, data, experience and resources.

Investigator partners include Children Hospital of Philadelphia, Seattle Children’s and Sanford Burnham Prebys Medical Discovery Institute.

Co-investigators include Baylor College of Medicine; Boston Children’s Hospital; Children’s Hospital of Colorado; Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center; National Human Genome Institute; Seattle Children’s Hospital; Tulane University Medical School; University of Alabama; University of Colorado, University of Minnesota Masonic Children’s Hospital; and University of Utah.

Wed, Sep 11 10:51am · Improving genomic data analysis - from soybeans to humans

Article by Colette Gallagher and Amy Clay-Moore

Daniel Wickland, Ph.D.

When Daniel Wickland,
Ph.D., was a predoctoral student at the University of Illinois at
Urbana-Champaign, he first worked to improve genomic data analysis for soybeans.
But soon he shifted his focus, bringing his computer programming and
informatics skills to work with Mayo Clinic and Illinois researchers to better
understand Alzheimer’s disease as part of the Mayo
Clinic and Illinois Alliance for Technology-Based Healthcare Research
Fellowship program
. Now he’s joined Mayo Clinic’s Department
of Health Sciences Research, applying his skills to help better understand the
underlying mechanisms driving breast cancer and to help develop immune-based
cancer therapies.

Here’s a closer look at how Daniel’s research fellowship led him to his new role at Mayo Clinic.

A program to distinguish genomic differences  

During the first part of his graduate program, Daniel worked with Illinois crop sciences professor Matthew Hudson, Ph.D., to map a gene in soybeans that controlled plant height and internode length.

Early in the project, the
team discovered the software they were using was not accurately identifying
differences between soybean genomes. While seeking a solution, Wickland
developed GB-eaSy, a program that dramatically increased the accuracy, speed,
and simplicity of genotyping-by-sequencing data analysis.

When Hudson encountered a similar data analysis need in his research at the National Center for Super Computing Applications (NCSA), he immediately thought of Wickland’s work with soybean genomes.

“As a result of Dan’s
prior work on variant calling software, and his interest in neuroscience from
his undergraduate days in the Illinois Neuroscience Program, I thought he would
be an excellent candidate for the Alzheimer’s disease sequencing project,” says
Hudson. “Although soybeans and humans are very different, the bioinformatics
problems involved were closely related,” says Hudson.

Hudson’s work with Liudmila
Mainzer, Ph.D
.,
senior research scientist at NCSA, and Yan
Asmann, Ph.D
.,
associate professor of biomedical informatics at Mayo, focused on improving genetic
variant calling software for human genomics targeted at Alzheimer’s disease.

The collaborators used
Blue Waters, NCSA’s petascale computer, to perform a vast number of comparisons
to troubleshoot the huge amount of genome data that Mayo was analyzing on
Alzheimer’s disease.

Although Wickland was nearing completion of his doctoral degree in crop sciences, he decided to transfer to the Informatics Ph.D. program and join this new project to focus on bioinformatics.

In the first year of his fellowship at NCSA, Wickland developed skills in high-performance computing and workflow programming. He mastered the complex workflows on Blue Waters necessary to analyze the data in several ways to determine the source of inconsistencies they were finding.

Over two years, the project used more than 600,000 node hours on Blue Waters, which is equivalent to a single server running continuously for almost 100 years.

“These intensive computing needs could not have been met without a resource like Blue Waters at NCSA” says Wickland. “Also critical to the success of this project were feedback and ideas from Dr. Hudson and Dr. Mainzer, my advisors at NCSA.”

Collaborating with Mayo Clinic experts to refine data analysis

In his second year,
Wickland worked at the Mayo Clinic campus in Florida and with Illinois
researchers to analyze genomic sequencing data of more than 10,000 cases and
healthy controls from the project.

“I received invaluable
guidance from my Mayo advisor, Dr. Asmann, and very helpful feedback from
renowned Alzheimer’s researchers at Mayo,” notes Wickland. “Working in these
two environments – Mayo Clinic and NCSA – exposed me to different methods and
ideas that strengthened my skills as a researcher.”

“He was ultimately able to determine that in this case, the problem did not lie in the software itself, but in the discrepancies between the data generated at the different participating institutions in the project,” says Hudson.

A new role

After receiving his doctoral degree, Wickland joined the Mayo Clinic Department of Health Sciences Research. He is working on a project that focuses on breast cancer immunogenomics with Dr. Asmann, Keith Knutson, Ph.D., professor of immunology, and Mark Sherman, M.D., professor of epidemiology and laboratory medicine and pathology.  

“I’m currently studying how the immune system
responds to tumor neoantigens (protein fragments found only on the surface of
cancer cells), how this response differs among individuals and among racial
groups, and how we can use this information to predict and enhance the
anti-tumor immune response in a personalized manner. This genomics research will
support efforts in the Center
for Individualized Medicine
to develop customized cancer vaccines targeted
to the specific neoantigens produced by a patient’s tumor,” says Dr. Wickland.

The Mayo-Illinois Alliance for Technology-Based Healthcare was founded in 2010 by Mayo Clinic and the University of Illinois – Urbana Champaign to advance research and clinical treatment options related to individualized medicine.

The latest advances in cancer care

Join us for Individualizing Medicine 2019 Conference: Precision Cancer Care through Immunotherapy and Genomics on Sept. 20-21, in Scottsdale, Arizona. 

The conference brings together experts from Mayo Clinic and across the country to present and discuss case-based approaches to using genomics and new immunotherapies that oncologists and their teams can bring back to their own patients.

Other key conference themes include:

  • CAR-T cell therapy
  • Clonality
  • Pharmacogenomics
  • Lineage Plasticity
  • National Cancer Institute match

Preview the conference program.

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Wed, May 15 8:00am · One year in, All of Us Research Program makes strides in diverse health research

All of Us Research Program Group

For far too long, biomedical research has been based on a small subset of the United States population, leading to prevention and treatment methods that are often one-size-fits-all. To address this issue, the National Institutes of Health All of Us Research Program is working to build a cohort of one million or more participant partners that reflects the diversity of the United States.

Program participants provide data and samples that will be broadly accessible to researchers for a wide range of studies. By taking into account individual differences, researchers will uncover paths toward delivering precision medicine — or individualized prevention, treatment, and care — for all of us.

May 6 marked one year from the program’s national launch. A Facebook live session,  “From Data to Discoveries: Creating a Research Program for All of Us,” was hosted by Francis Collins, M.D., Ph.D., director, National Institutes of Health. Dr. Collins identified the building blocks of a meaningful research program, including an engaged and diverse participant community, and forecasted the program’s scientific possibilities.

1st Year Milestones – All of Us Research Program Biobank at Mayo Clinic

Mayo Clinic is one of more than 100 organizations across the United States that is funded by the National Institutes of Health All of Us Research Program. In 2016, Mayo Clinic was awarded $142 million in funding over five years by the National Institutes of Health to serve as the program’s biobank.

“The All of Us Research Program biobank at Mayo Clinic has the capacity to store more than 35 million biospecimens.”

Since the launch of the program on May 6, 2018 several milestones have been reached.

“The All of Us Research Program biobank at Mayo Clinic has the capacity to store more than 35 million biospecimens,” says Stephen Thibodeau, Ph.D., co-principal investigator of the All of Us Research Program biobank funding award. “It is currently storing more than 3 million frozen vials from consented participants and has capacity to process samples from up to 1,500 participants per day.”

In addition to increasing lab space in Rochester and on the Mayo Clinic campus in Florida, the team ramped up equipment, built up its technical infrastructure, and has established a business continuity plan in the case of a catastrophic event.

“We expanded our laboratory operation to fully automate sample processing and sample storage,” says Mine Cicek, Ph.D., co-principal investigator and laboratory director, Mayo Clinic Biorepositories Program, Center for Individualized Medicine. “Our team continually monitors multiple indicators related to incoming specimen quality control events and provides feedback to enrollment sites.”

From hiring support staff to maintaining an education plan for program partners to providing 24/7 customer support the All of Us Research Program Biobank at Mayo Clinic works to enable precision medicine research to improve the health of the nation.

More information

For more information, visit the All of Us Research Program website.

Watch the Facebook Live session celebrating the program’s one-year mark and hear from National Institutes of Health Director Francis Collins, M.D.:

Dr. Thibodeau is the David F. and Margaret T. Grohne Director, Mayo Clinic Biorepositories Program, Center for Individualized Medicine.
This work is supported under NIH funding award RFA-PM-16-004. 

“All of Us” is a registered service mark of the U.S. Department of Health and Human Services. For more information, visit http://www.JoinAllofUs.org and http://www.allofus.nih.gov.

Tue, Apr 23 10:07am · Editorial: Why DNA sequencing is an effective tool for patient care

By Keith Stewart, M.B., CH.B.

For the past 30 years, I’ve been fortunate enough to work with and help many patients. But over that time, I’ve also met people who did not respond to therapy or had significant side effects, while others had marvelous responses. Cases like these show a clear need for personalized medicine. Fortunately, I’ve also seen the adoption of a new technology that allows us to gain unprecedented insight into a patient’s specific needs: DNA sequencing.

Dr. Keith Stewart, Medical Director, Mayo Clinic Center for Individualized Medicine
Dr. Keith Stewart

Everyone has their own unique sequence of DNA — a molecular fingerprint — that determines personal characteristics like height, hair and eye color, and risk for disease. Research has shown us that insights into a person’s DNA sequence allows us to personalize their health care to their own genetic makeup to better meet their needs.*

In the past decade, we’ve seen exponential growth in DNA sequencing technology and an expansion of its use in medicine.* In 2012, Mayo Clinic adopted DNA sequencing as a major tool in individualized medicine by using targeted gene panels and whole exome sequencing. We started by looking for actionable targets in patients with advanced cancers (unique features of a tumor that can make one therapeutic drug particularly effective). We quickly expanded this approach beyond cancer by opening clinics that helped to diagnose rare and undiagnosed diseases.

Rare and undiagnosed diseases

Our patients come from around the world, often seeking a diagnosis for a rare disease that no other doctor or clinic has been able to provide. Whole exome testing sequences more than 20,000 genes. That represents about one percent of a patient’s DNA — the part that we today understand contains the majority of useful genetic information that can pinpoint an illness. Patients can get their DNA mapped and have results within a few weeks to apply to their treatment plans. Prenatal screening could be made less invasive and more comfortable for patients with DNA sequencing, so we did that too. What we found was that DNA sequencing greatly expanded our ability to help patients by providing them with more informed and often more effective health care.

Treatment of cancers

One area where we’ve found DNA sequencing to be particularly effective is in the treatment of cancers.* One example that comes to mind is that of a young girl who had acute lymphoblastic leukemia, an aggressive form of blood cancer. None of the mainline therapeutic strategies had worked for this patient. But thankfully, DNA sequencing identified mutations in the cancer that could be leveraged. It’s clear from this example — and from many more like it — that DNA sequencing is a valuable tool in designing personalized treatments for some cancer patients. But there’s also benefit in potentially preventing the development of cancer in the first place. It’s estimated that between 10-15% of cancers involve a heritable mutation.* Current screening methods used to identify people who are at risk of developing cancer may miss up to 50% of heritable cancers. That leaves a lot of room for improvement, and DNA sequencing is proving to be a valuable tool in this regard.

Prevention of adverse drug reactions

Another valuable application is in the prevention of adverse drug reactions. It’s probably no surprise to learn that some people respond to medicine differently compared to others. In some of these cases, people may even have an unwanted or dangerous response to the drug. These are known as adverse drug reactions, and it’s estimated that approximately 1.5 million of them happen each year in the U.S., resulting in a thousand deaths annually. Research has shown us that some people are genetically predisposed to experiencing an adverse drug reaction, which means there’s an opportunity for DNA sequencing to help identify those individuals and help guide their treatment away from unnecessary risks.

My personal experience

It so happens that I’m one of those individuals. Through DNA sequencing, I found that I should avoid a number of medicines. Most of them are drugs that I will probably never need, but some of them I might. Thanks to this testing, I know what those are and can act accordingly in the future. This brings me to a benefit of DNA sequencing that I think we often overlook. I had my DNA sequenced and got information about my carrier status, potential drug reactions, and a number of health conditions. This was important to me because I have family members whose lives have been affected by a heritable genetic condition. I’ve found that having my DNA sequenced empowers me with knowledge — knowledge that I can use in the future to help guide medical treatment away from potentially dangerous drugs, and maybe even help my health care providers save valuable time if they’re ever looking for a diagnosis. So it’s not just a result that helps me stay informed today; it’s something I will likely use for the rest of my life. To be sure, DNA sequencing is not without its limitations.* When we first started in 2012, we were limited by the cost of sequencing and the time it took to receive and interpret a patient’s results. There is still so much we don’t know about genetics, and research is ongoing to determine how DNA sequencing is best applied. But this research has unlocked new avenues for improving outcomes in recent years, and I strongly believe this trend will continue. In the midst of this DNA sequencing revolution, I’ve had the unique opportunity to explore the field as a researcher, a physician, and an administrator, and I can tell you what an exciting time this is to be learning more about your genetics. My experience has shown me that DNA sequencing is not just a thing of the future — it’s a very real and impactful tool of the present.

Keith Stewart, M.B., CH.B., is the Carlson and Nelson Endowed Director of the Mayo Clinic Center for Individualized Medicine.

1. Manolio, Teri A. et al. “Implementing Genomic Medicine in the Clinic: The Future Is Here.” Genetics in Medicine 15.4 (2013): 258–267. PMC. Web. 21 Sept. 2018.   6. https://www.cancer.gov/about-cancer/causes-prevention/genetics

2. Delaney, Susan K. et al. “Toward Clinical Genomics in Everyday Medicine: Perspectives and Recommendations.” Expert Review of Molecular Diagnostics 16.5 (2016): 521–532. PMC. Web. 21 Sept. 2018.

3. Bryce, Alan H., et al. “Comprehensive Genomic Analysis of Metastatic Mucinous Urethral Adenocarcinoma Guides Precision Oncology Treatment: Targetable EGFR Amplification Leading to Successful Treatment With Erlotinib.” Clinical Genitourinary Cancer, vol. 15, no. 4, 2017, doi:10.1016/j.clgc.2016.11.001.

4. Torkamani, Ali et al. “High Definition Medicine.” Cell 170.5 (2017): 828–843. PMC. Web. 21 Sept. 2018.

5. Borad, Mitesh J. et al. “Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.” Scientific Reports 6 (2016): 25. PMC. Web. 21 Sept. 2018.

6. https://www.cancer.gov/about-cancer/causes-prevention/genetics

Mon, Apr 8 8:00am · Genetic test solves mystery of family bleeding disorder

The Riggs family had a bleeding disorder that spanned three generations and affected the health of multiple family members. They never knew the cause of it, the long term risks associated with it, or the impact it may have on future generations — until a genetic test revealed the answer.

Finding the clues to the mystery of the family bleeding disorder began when Mallory’s father, Timothy, came to Mayo Clinic for cardiovascular surgery. Before surgery he met with Mrinal Patnaik, M.B.B.S., a Mayo Clinic hematologist, specializing in the diagnosis, treatment and prevention of blood diseases.

“I looked at his medical records and it didn’t make sense,” says Dr. Patnaik. “I told him we didn’t know what exactly he had but the fact that three generations in his family all have abnormally low blood platelets makes this very likely to be something inheritable.”

Dr. Patnaik ordered a whole exome sequencing test for Timothy and Mallory. Whole-exome sequencing tests more than 20,000 genes. That represents about one percent of a patient’s DNA – the part containing the majority of useful genetic information that can pinpoint an illness.

The test showed that Timothy and Mallory had a genetic variation in a gene called RUNX1 causing them to have an abnormally low blood platelet count (thrombocytopenia). Some symptoms of a low blood platelet count may include easy or excessive bruising, superficial bleeding, and prolonged bleeding.

“This gene mutation not only causes low blood platelets, but increases the risk for certain blood cancers to develop overtime like myelodysplastic syndrome and acute myelogenous leukemia,” says Dr. Patnaik.

According to Mallory having the answers put her at ease in caring for her son Sawyer who was diagnosed with the same bleeding disorder at 10-months-old. Today, Sawyer is five-years-old and the busiest and most active of her three boys.

“Now that we have answers I can let Sawyer be himself, and be that active little boy and do all of the things that he loves and enjoys doing,” says Mallory. “We can let our kids be kids, wrestling , playing and climbing and not being so concerned about all of the what ifs.”

According to Dr. Patnaik, a genetic test for this family was valuable in finding the answer and providing hope to the family.

“Having a correct diagnosis impacts the family’s medical care today and in the future,” says Dr. Patnaik. “We now understand how to treat them for surgeries, the family has a screening tool and we are monitoring them annually.”

Patients like the Riggs family with rare and undiagnosed conditions can spend years meeting with multiple health care providers to seek a diagnosis. They often try a myriad of treatment plans that aren’t appropriate and never find the answer to what is causing their disorder.

Helping find the answer for the Riggs family inspired Dr. Patnaik to start the first-of-its-kind Premyeloid and Bone Marrow Failure Disorder Clinic so other patients could benefit from precision diagnosis and new individualized therapies.

Mayo Clinic Premyeloid and Bone Marrow Failure Disorder Clinic

  • Offers genetic testing for the early detection of rare blood disorders and bone marrow cancers
  • Uses DNA sequencing and conducts research to solve cases with unexplained low blood counts
  • Allows for early intervention in which providers can define disease management plans
  • Identifies through research how each patient’s unique genetic makeup impacts these disorders and could lead to new individualized therapies

For more information visit ClinicalTrials.gov.

  • Search for NCT02958462 or via Google by title.
  • The clinical service and the NIH-listed research study will appear.
  • Patients can have the clinical service without doing any research.

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Mon, Jan 14 7:00am · Using brain organoids to uncover causes of neuropsychiatric disorders

Mayo Clinic and Yale University collaborated in a study published in Science to create a new model for studying neuropsychiatric disorders in early human brain development. This unique collaboration brought together Mayo Clinic’s team-based, patient-centered research with Yale researchers to discover and analyze the genetic mechanisms that may cause these disorders.

The Mayo Clinic team, led by biomedical scientist Alexej Abyzov, Ph.D., used the organoid model to analyze artificially grown cells that resemble the brain (brain organoids) to outline groups of developmental genes and regulatory elements related to the cause of autism.

Researchers know that genes implicated in neuropsychiatric disorders are active in the human fetal brain. However, systematic and comprehensive studies are hampered due to the difficulty in getting fetal brain tissue. According to Dr. Abyzov, the power of organoids is that they can be created from the skin cells of any individual.

“Using brain organoids helps to uncover the genetic underprints of these disorders and helps identify functional elements that may drive disease onset,” says Dr. Abyzov. “Our results suggest that organoids may reveal how noncoding mutations contribute to the cause of autism. By understanding the cause of autism this research may lead to assessing the personal risk for other neuropsychiatric disorders.”

The research team set out to discover gene-regulatory elements and chart their dynamic activity during prenatal human brain development, focusing on enhancers (the short region of DNA), which carry most of the weight upon regulation of gene expression.

“Over a period of time we modeled human brain development using human-derived brain organoids and compared those organoids to fetal brain tissue that had the same genotype,” says Dr. Abyzov. “This study validated that using brain organoids is a suitable model system for studying gene regulation in human embryonic brain development, evolution and disease.”

The research team is planning a larger study using organoids to compare regulation and expression during development for individuals with autism.

“This model has the potential to offer a personalized approach to each patient with autism,” says Dr. Abyzov.

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