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Sep 19, 2017 · CARING FOR KARTER--Genetic sleuths never give up hunt to identify Minnesota boy's condition

Mayo Clinic’s functional genomics team never gave up hunt to identify Karter Malcomson’s rare condition.

Karter Malcomson coos and swivels his head when he hears his name in his mother’s reassuring voice.

“You know we’re talking about you, don’t you?” Karter’s mom, Kerrie, says. “Karter is a very happy boy. He’s very content. He’s very interested in everything, especially people. He’s definitely a people person.”

His father, Zane, spins Karter upside down on his lap and smiles ensue.

“Kerrie always says how much Karter loves me,” Zane says. “I notice it when I come home from work and he reaches out to me and wants me to hold him. We have a great bond.”

Karter just turned 2 but is delayed in growth and cognitive abilities. He also has a surgically made hole in the front of his neck into his windpipe to aid in breathing.

“He’s obviously very small, the size of a 6- or 8-month-old, and he doesn’t walk. He doesn’t do any of that normal 2-year-old stuff,” Kerrie says.


Kerrie and Zane knew before Karter was born at Mayo Clinic in Rochester, Minnesota, he would have health concerns. Karter had stopped growing in the womb and was growing extra fingers, a sign of a genetic disorder. He spent three months in the newborn intensive care unit.

As Karter began his life, his parents worried.

“Before his diagnosis, the wondering was the worst — when you just don’t know. You’re like, ‘How do I help my child? I don’t know what I’m doing. I don’t even know what he has,'” Kerrie says.

But Karter’s symptoms didn’t place him in any well-defined rare disease category. Even at an institution that sees more than 1.3 million people each year across a wide spectrum of complex conditions, his doctors realized that there was something different about Karter’s rare genetic disorder.

The Mayo Clinic Department of Clinical Genomics consults with physicians who treat patients like Karter, whose case was handled by clinical geneticist Pavel N. Pichurin, M.D. Dr. Pichurin and his colleagues try to determine the genetic disorder and provide patients with a diagnosis through review of scientific literature and tests.

But what if, after all testing is complete, the symptoms that a person has don’t match up with the results, or the results are inconclusive? What happens if there is no answer? What happens to cases like Karter’s?


Charu Kaiwar, M.D., Ph.D., dreads getting the question at social events: “What do you do for a living?”

“It’s not an easy answer. It would probably be an essay,” she says.

That’s because Dr. Kaiwar, a research fellow, is part of a group that reviews the cases of people who have exceedingly rare or undiagnosed disorders like Karter’s. Dr. Kaiwar is one of the members of the functional genomics team at Mayo Clinic’s Center for Individualized Medicine. The group includes a team of experts in lab science, data crunching and genetics who are all working together to find genomic-based answers to some of the most puzzling patient questions.

This often means sifting through the literature of thousands of cases and information on thousands of genetic variants in a person’s body that may — or most likely may not — be significant.

“It’s so complicated,” Dr. Kaiwar says. “But there’s so much potential here for the future.”

That quest for an answer by the staff and patients, who typically have bounced around from different specialists in other health care organizations, can become an all-consuming pursuit.

“We are usually the last resort. We could spend hours or months on it,” says research fellow Filippo Pinto e Vairo, Ph.D. “If we are not doing this, it’s almost impossible that the physician or genetic counselor can spend the time to do it.

“That’s what motivates us. We are a team that works together with different backgrounds. We know we can share experiences and learn from each other and provide something to patients.”

The team, which is reviewing about 50 cases at any given time, solves approximately 30 percent of them. And the percentage is rising.

“Many patients with an unknown genetic disorder will have spent years managing their health problems while also trying to determine what the disease actually is,” says Margot A. Cousin, Ph.D., a health sciences research fellow. “To be done hunting for the answer, it provides a lot of comfort. These patients and families are finally able to move on from the constant wonder about the cause of their disease and focus on what they might now be able to predict.”


Zane, Karter and Kerrie waited for Karter’s test results while Mayo Clinic’s functional genomics team investigated. The team worked to verify variants in Karter’s C2CD3 gene that were driving his disease, which physicians ultimately diagnosed as oral-facial-digital syndrome, type 14.

Nicole J. Boczek, Ph.D., was one of the leaders of Karter’s care behind the scenes for the functional genomics team. She never met the happy-go-lucky boy, but spent months working on his case.

“Karter’s testing came back with two interesting variants, both of them within the same gene: C2CD3,” says Dr. Boczek, a molecular geneticist. “Only one paper had ever been published regarding this gene related to disease. It overlapped pretty well with Karter’s symptoms. But we had to take these findings to the next level and prove these variants of uncertain significance were related to Karter’s symptoms.”

To do that, Dr. Boczek and the team did additional laboratory testing to show that these genetic variants were affecting protein development and driving Karter’s disease. Through the team’s work, they homed in on a diagnosis — oral-facial-digital syndrome.

Oral-facial-digital syndrome has at least 13 types, according to the U.S. National Library of Medicine. Karter’s case didn’t fit in the other 13 categories and was diagnosed as type 14.

“There are nine individuals reported ever in the literature with this condition stemming from this gene,” says Dr. Boczek. “Since we’ve worked on Karter’s case, we now are contributing to the literature with four more cases. It is really rare, but it is inspiring.”


Kerrie says finding an answer to Karter’s condition has brought her peace, while Zane said he believes the information will help them in the future.

“There’s so much potential. His doctors can only guess at what he’ll be able to do, and he continues to surprise us every day,” Zane says. “It gives us hope for the future.”

Karter’s breathing, sleep and vision issues are managed by a comprehensive treatment plan. He also works with a physical therapist weekly. Kerrie raves about the compassionate care Karter and her family have received each step along the way.

“I really have grown to love the care team he has now,” Kerrie says. “I don’t have to worry.”

And Karter, who listens intently and claps intermittently to a musical toy in his living room, has proven the ability to exceed any preconceived expectations.

Kerrie and Zane hope one day Karter will be able to meet milestones such as crawling, changing positions and maybe walking. But for now, they’re happy that he’s happy.

“Karter is a happy boy, not someone with health issues,” Kerrie says. “He’s very personable. He’s everybody’s best friend.”


Genetics continues to be at the forefront of research, patient diagnosis and treatment. But how do each person’s genes and genetic variants factor in his or her care?

Consider the example Nicole J. Boczek, Ph.D., uses when she discusses the role of genetics:

“There are trillions of cells in someone’s body, and all of them have a copy of a ‘recipe book’ (your DNA). That recipe book helps each cell make all the different recipes to help us live our lives every single day, making each cell function, helping our hearts beat, making our digestive system work properly, and so on.

“There are typos in every person’s recipe book. A lot of times, these typos are small, maybe a word is spelled wrong, but it doesn’t change the content. Your body can still read and understand the recipe and everything is fine. But if there’s a typo at a key point, such as changing the baking temperature from 350 degrees Fahrenheit to 550 degrees Fahrenheit, this can completely change the end product and may cause a significant problem.

“So our goal is to try and find all of the typos in each recipe — or gene — and see which ones are actually important and make significant changes to the recipe to establish if there’s going to be a problem.”


In the late 1990s before he earned a doctoral degree, Eric W. Klee, Ph.D., became hooked on an emerging field of science.

Dr. Klee, from a family of medical doctors, still wasn’t sure whether to pursue an M.D. when mentor Franklyn G. Prendergast, M.D., Ph.D., told him that the future of medicine would be in a developing field of study.

“I like computers. I like technology, but I also liked medicine,” Dr. Klee says. “And Dr. Prendergast said, ‘There’s a field in science called bioinformatics. It doesn’t really exist yet, and it won’t exist for a few years, but when it does, it’s going to be important for decades.'”

Dr. Klee took the leap of faith that the numbers would work out in his favor, graduating with a Ph.D. in health informatics/bioinformatics. He joined Mayo Clinic in 2005 as one of the first employees hired with a degree based in the emerging field that applies large amounts of health data into individualized tests and treatment plans for patients.

In 2012, Mayo Clinic created the Bioinformatics Program under the direction of the Center for Individualized Medicine. The center also launched the Individualizing Medicine Conference to provide a space for collaboration aimed at better incorporating genomic information into patient care.

At the conference Dr. Klee sought out then-center director Gianrico Farrugia, M.D., and associate administrator Scott A. Beck to propose the idea of a team that could dig deep into the functional science of genetic changes on behalf of patients with undiagnosed genetic disorders. Benefactors helped the concept gain seed funding, and the functional genomics team blossomed.


Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. This article was originally featured on the philanthropic site “You Are…the campaign for Mayo Clinic.”

Sep 7, 2017 · MUNEER SATTER--Genes made personal through foundation's support

Muneer Satter’s first interest in medicine wasn’t rooted in genomics. It was in seeing the health care needs of his loved ones and of the world’s most vulnerable. In his professional life, before making investments in biotech, he sought out the opinions of expert doctors at Mayo Clinic.

“The more I talked to doctors, the more I started gravitating there,” the Chicago investor says. “That’s when I realized biotech was going to be a big deal.”

The Satter Foundation is a Principal Benefactor to Mayo Clinic’s mission, supporting the Center for Individualized Medicine‘s efforts to discover, translate and apply genomic medicine services and products to each patient.


IM 2017 October 9-11thThe foundation’s support helped the center launch the Individualizing Medicine Conference, which brings together a who’s who of leaders in genomic sciences each fall.

In October 2016, more than 1,300 attendees representing health providers, industry and the public came to Rochester, Minnesota, to explore ways to accelerate the advances in genomic medicine into everyday practice.

In its first five years, the conference has drawn an international audience and well-known presenters in the field, including leaders from the National Institutes of Health, the American Society of Clinical Oncology and direct-to-consumer companies such as Helix, 23andMe and Human Longevity.

The past two years, Cathy Wurzer, the host of Minnesota Public Radio’s “Morning Edition,” has hosted the event.

“I’m amazed by the brainpower in the room both in terms of speakers and attendees,” Cathy says. “It is clear to me that Mayo, because of its reputation, can bring in top-notch genomics researchers and other innovators in the field in order to have in-depth, yet accessible conversations.”


For Muneer, the commitment to health and education is part of the Satter Foundation‘s commitment to better the world for all its citizens. He and his wife, Kristen Hertel, formed the foundation in 1997 with the vision of a world where all people — no matter where or in what circumstances they are born — have the resources and opportunities to live a free, educated, prosperous and healthy life.

But the Satter family’s first interactions with Mayo Clinic came due to an illness where the family saw firsthand the Mayo Clinic Model of Care at work.

“Mayo is deeply committed to people,” says Muneer. “Every time I’ve been there, the service level has been amazing. It’s very, very different from most hospitals. It’s really an exceptional experience — a personal experience. Things run on time; things get done correctly. Mayo Clinic works as a team; they talk to each other.

“But, most of all, people care. You feel the caring and compassion for people who are really sick from the moment you come in. It’s a special place.”


Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. This article was originally featured on the philanthropic site “You Are…the campaign for Mayo Clinic.”

Aug 10, 2017 · TOGETHER TRIAL--An individualized strategy for stopping organ rejection

Mayo Clinic’s Center for Individualized Medicine is collaborating with a molecular diagnostics company to monitor patients after an organ transplant and improve the efficacy of immunosuppressant drugs by tailoring treatment to an individual’s genome.

The effectiveness of immunosuppressant drugs is governed by a number of factors, but a major contributor is an individual’s genome. The genes that make up each person’s genome direct how a drug is metabolized and how it stimulates the immune system to accept the transplant.

While these drugs help a transplanted organ continue to function, they tax the rest of the body. For transplant patients, it is essential to understand the appropriate regimen of anti-rejection medications. Mayo Clinic’s Center for Individualized Medicine is collaborating with a molecular diagnostics company to monitor patients after an organ transplant and improve the efficacy of these drugs by tailoring the treatment to an individual’s genome through the TOGETHER trial. The initial focus is on immunosuppressant therapies for 250 kidney transplant recipients.

“Genomic analysis of blood can reveal early signs of rejection in transplanted kidneys,” says principal researcher Mark D. Stegall, M.D., the James C. Masson Professor of Surgery. “The potential clinical utility is to be able to monitor for rejection more frequently than is possible with surveillance biopsies and to individualize immunosuppression in transplant recipients.”

Among this study cohort, kidney transplant patients will have genomic testing at five intervals throughout their first postoperative year. These data points may help transplant care teams fine tune immunosuppression drug regimens and improve patient outcomes.

“The promise of individualized medicine is that we can now use information found in a patient’s own genetic code to provide better, more personalized answers about their medical care. Through important efforts such as the TOGETHER trial, we can and will make that promise more of a reality for our transplant patients,” says Alexander S. Parker, Ph.D., the Cecilia and Dan Carmichael Family Associate Director for the Center for Individualized Medicine at Mayo Clinic in Jacksonville, Florida.


If the science and medical practice of individualized medicine are of professional or personal interest to you, consider attending the Individualizing Medicine Conference, October 9-10, 2017, in Rochester, Minnesota.

You can find out about more clinical trials on Mayo’s clinical trials website.

Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. This article was originally featured on the philanthropic site “You Are…the campaign for Mayo Clinic.”



Idividualizing Medicine Conference 2017
William A. Gahl, M.D., Ph.D.William A. Gahl, M.D., Ph.D., Clinical Director of the National Human Genome Research Institute, will speak about the NIH Undiagnosed Diseases Program and its expansion.

“Desperate for answers” is how Dr. Gahl describes many patients and families he sees with puzzling disorders. The program aims to provide answers to patients who have suffered for years with mysterious conditions eluding diagnosis. Dr. Gahl’s work has played a significant role in advancing medical knowledge about rare and common diseases.

Read more via the Individualized Medicine Blog.

Register Today


Although there are thousands of diseases that are individually rare, they are collectively common and can affect millions of patients worldwide. Studying collaboratively across research and clinical practice leads to better tools for diagnosis and treatments.

Presenting advancements in genomic medicineConference Sessions on Rare Diseases:

Register Today

Are you an early career investigator? The Brandt Family Scholars Fund has travel scholarships to support your attendance at the conference. Applicants must be attending United States institutions and submit an abstract and letter of interest by June 30th, 2017.

More information is available online.

Visit for more information.

Register Today


This activity is eligible for AMA PRA Category 1 credit., CPEs for pharmacists, and pending CEUs for genetic counselors.

Mayo Clinic College of Medicine and Science is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

For questions, contact 507-266-2633 or email

Sep 14, 2015 · Human antibody can delay Lou Gehrig’s Disease in two mouse models

spinal neurons 1Researchers at Mayo Clinic and the University of Minnesota have successfully used a single dose of a natural human antibody to delay degeneration of spinal cord neurons in two distinct mouse models of amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). The study, published in Disease Models & Mechanisms, suggests new possible therapies for patients with ALS, the authors say.

“These findings provide great hope for patients with ALS,” says Moses Rodriguez, M.D., Neurology, senior author of the study. “In human studies, the antibodies may be given at regular intervals rather than as a single dose, thus potentially increasing the chance for greater effect.”

ALS affects more than 30,000 Americans, according to the ALS Association. The condition attacks motor neuron cells in the brain and spinal cord that control voluntary muscle activity like moving, speaking, breathing and swallowing. These cells degenerate and gradually die, causing progressive loss of muscle movement and eventual death from respiratory failure. There is no cure for ALS, so current treatments focus on slowing the development of symptoms and preventing unnecessary complications.

In the study, the researchers looked at a natural human monoclonal antibody similar to one that has been shown to slow multiple sclerosis, another neurodegenerative disease, in mice. The monoclonal human antibody, known as rHIgM12, binds to the surface of neurons and promotes robust process outgrowth, which may lead to the protection of neurons.

The investigators tested the effects of rHIgM12 in two genetic-based models of human ALS in mice. In both mouse models, a single dose of antibody prolonged survival, delayed the onset of neuron degeneration and weight loss, and preserved spinal cord axons and anterior horn neurons.

According to the authors, the antibody’s effectiveness in multiple mouse models of neurodegenerative disease implies a broad ability to protect neurons — a key criterion in screening potential drugs for clinical trials in humans. The next step is to seek funding for a phase 1 clinical trial to obtain safety data in humans, says Dr. Rodriguez.

Co-authors include:

  • Xiaohua Xu, M.D., Ph.D., Mayo Clinic
  • Aleksandar Denic, M.D., Ph.D., Mayo Clinic
  • Arthur Warrington, Ph.D., Mayo Clinic
  • Bharath Wootla, Ph.D., Mayo Clinic
  • Louisa Papke, Mayo Clinic
  • Laurie Zoecklein, M.S., Mayo Clinic
  • Luke Jordan, University of Minnesota
  • Nathan Wittenberg, Ph.D., University of Minnesota
  • Daehan Yoo, M.E., University of Minnesota
  • Jonah Shaver, Ph.D., University of Minnesota
  • Sang-Hyun Oh, Ph.D., University of Minnesota.

The study was supported by grants from the National Institutes of Health (R01 GM092993, R01 NS048357 and R21 NS073684); the National Science Foundation Faculty Early Career Development Program Award; the Minnesota Partnership Award for Biotechnology and Medical Genomics, a research collaboration of Mayo Clinic and the University of Minnesota; the National Multiple Sclerosis Society (CA1060A); and the Mayo Clinic Center for Clinical and Translational Science. Study guidance was provided by the nonprofit Prize 4 Life.


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