Top Stories - Genetic Diseases

A mouse model of multiple hereditary exostoses (MHE), a rare bone disorder, exhibits autism-like social deficits. Shown here is a comparison of nest-building abilities—one measure of social behavior—by normal and autistic MHE mice.
Rare bone disorder reveals new...

Sanford-Burnham researchers discover the molecular basis of autistic symptoms in children with a...

New therapy for Corinna’s inherited disorder helps her walk for the first time.
My moment with Corinna

At our Rare Disease Day Symposium just three months ago, I met a young girl with hypophosphatasia...

Mayor Hall of Bakersfield cuts the ribbon to open Salon Gianna. Beside him is Gianna, with Dr. Hudson Freeze and her mother, Natalie. On the right are Rocket’s parents, Mia and Taylor Williams, and Gianna’s father, David.
A rare approach for a rare...

The family that owns Salon Gianna, a beauty salon in Bakersfield, California, is on a mission find a...

Dr. José Luis Millán
Chance encounter saves a...

In 2008, a young child, known simply as Baby Amy, was flown from her home in Ireland to Winnipeg,...

Drug discovery case study: high-throughput screening of TNAP

by on April 11, 2012 at 11:52 am | 0 Comments
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Presence of calcium deposits in a mouse aorta, as revealed by alizarin red staining.

Presence of calcium deposits in a mouse aorta, as revealed by alizarin red staining.

Editor’s note: this is the second in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the first post here.

Calcification of the medial layer of arteries is increasingly recognized as an important clinical problem. Medial vascular calcification (MVC) is the major cause of morbidity and mortality in generalized arterial calcification of infancy (GACI), and contributes to cardiovascular deterioration in Kawasaki disease (KD), chronic kidney disease (CKD), as well as in diabetes, obesity, and aging. MVC is thought to result from decreased circulating levels of the mineralization inhibitor, inorganic pyrophosphate (PPi).

Researchers at Sanford-Burnham have revealed that the development of MVC in mouse and rat models is accompanied by up-regulation of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme whose primary function is to hydrolyze PPi, and thus, crucial in determining where mineralization occurs. Preliminary data have proven that upregulation of TNAP is sufficient to cause MVC and Sanford-Burnham scientists have developed potent drug-like inhibitors of TNAP.

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Rare bone disorder reveals new insights into autism

by on March 12, 2012 at 12:00 pm | 0 Comments
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A mouse model of multiple hereditary exostoses (MHE), a rare bone disorder, exhibits autism-like social deficits. Shown here is a comparison of nest-building abilities—one measure of social behavior—by normal and autistic MHE mice.

A mouse model of multiple hereditary exostoses (MHE), a rare bone disorder, exhibits autism-like social deficits. Shown here is a comparison of nest-building abilities—one measure of social behavior—by normal and autistic MHE mice.

Children with multiple hereditary exostoses (MHE), an inherited genetic disease, suffer from multiple growths on their bones that cause pain and disfigurement. But beyond the physical symptoms of this condition, some parents have long observed that their children with MHE also experience autism-like social problems.

Buoyed by the support of these parents, researchers at Sanford-Burnham recently used a mouse model of MHE to investigate cognitive function. They found that mice with a genetic defect that models human MHE show symptoms that meet the three defining characteristics of autism: social impairment, language deficits, and repetitive behavior. The study, published online the week of March 12 in the Proceedings of the National Academy of Sciences, also defines the molecular and physiological basis of this behavior, pinpointing the amygdala as the region of the brain causing autistic symptoms.

“There is growing evidence that many autistic people have related genetic defects, or defects that are exacerbated by this one,” said Yu Yamaguchi, M.D., Ph.D., professor in the Sanford Children’s Health Research Center at Sanford-Burnham. Yamaguchi led this study, along with colleagues Fumitoshi Irie, Ph.D. and Hedieh Badie-Mahdavi, Ph.D.

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Exciting clinical trial news for children with inherited bone disease

by on March 8, 2012 at 9:58 am | 0 Comments
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Enyme replacement therapy ENB-0040 enhances bone formation in patients with hypophosphatasia.

Enyme replacement therapy ENB-0040 enhances bone formation in patients with hypophosphatasia.

José Luis Millán, Ph.D. and his lab have studied hypophosphatasia, an inherited disease that makes bones dangerously fragile, for the past 15 years. The researchers developed a mouse model of the disease—mice that, like their human counterparts, lack an enzyme called alkaline phosphatase. Then, just about five years ago, scientists from Enobia Pharma approached Millán. They had developed an enzyme replacement therapy called ENB-0040 and they needed someone who could help them test it—someone with a model and with extensive knowledge of hypophosphatasia and the alkaline phosphatase enzyme. So Millán and his team administered it to their mice. Mice with hypophosphatasia usually survive for 20 days at most. When the treated mice were alive at day 21, Dr. Millán knew they were onto something promising.

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Mason’s wish

by on March 2, 2012 at 9:09 am | 4 Comments
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Mason with Dr. Hudson Freeze (left) and philanthropist T. Denny Sanford, big supporter of children's health research, at Sanford-Burnham's third annual Rare Disease Day Symposium

Mason with Dr. Hudson Freeze (left) and philanthropist T. Denny Sanford, big supporter of children's health research, at Sanford-Burnham's third annual Rare Disease Day Symposium

Ten year-old Mason Barto is a sweet Pennsylvania fifth grader almost like any other. Except that he’s lived with a tracheotomy, a permanent feeding tube, and a number of other health problems since birth. Mason’s condition was inherited, but for most of his life no one could pinpoint the genetic cause of his health problems. They didn’t even have a name for it.

Then, a few months ago, Sanford-Burnham’s Dr. Hudson Freeze and his team finally discovered the genetic defect underlying Mason’s health problems and diagnosed him with what’s called a congenital disorder of glycosylation (CDG). In other words, Mason has a mutation in a gene that directs glycosylation—the process by which cells coat proteins with sugars. Lack of sugars disrupts cell growth, differentiation, and communication. There are several different types of CDG and symptoms and severity can vary widely.

While it doesn’t mean there’s an immediate cure for Mason, he is now taking a simple sugar therapy and is beginning to show early signs of improvement. The finding also gives new hope to other children living with this condition.

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Today is Rare Disease Day

by on February 29, 2012 at 10:54 am | 0 Comments
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RDD

Rare diseases are roughly defined as conditions affecting fewer than 200,000 people in the United States. Although a relatively small number of people are diagnosed with each individual disorder, there are 6,000 different rare diseases. Added together, these affect 1 in 10 Americans—30 million people.

Today, February 29, is the rarest day of the year and also Rare Disease Day. Last week, we held our 3rd annual Rare Disease Symposium. Today, there are events being held all over the U.S. and the world. Here are just a few:

National Institutes of Health (NIH) is holding a day-long celebration and recognition of the various rare diseases research activities supported by the NIH.

National Organization for Rare Disorders (NORD) will be live-streaming the Rhode Island Rare Disease Foundation Awareness event taking place 6:00-8:00 p.m. ET today in Cranston, RI. NORD is also sponsoring a Handprints on the Hill campaign to encourage everyone to join us in sending an important message to President Obama, members of Congress, and other elected officials.

For more information, check out:
Pictures from Sanford-Burnham’s Rare Disease Day Symposium 2012
Keynote talk by Dr. Eric Green, director of the National Human Genome Research Institute
Video, blog posts, and more from Sanford-Burnham’s Rare Disease Day Symposium 2011
Rare disease research at Sanford-Burnham

5 research areas bringing us closer to personalized medicine

by on February 24, 2012 at 2:28 pm | 2 Comments
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Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH

Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH

At Sanford-Burnham’s 3rd annual Rare Disease Day Symposium, held today in La Jolla, Calif., keynote speaker Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH, spoke about genomic medicine. Sometimes called “personalized medicine,” or even “precision medicine,” Dr. Green defined this revolutionary field as the idea that health care can be tailored to the individual based on his or her own genomic information.

Dr. Green was there when the human genome was first sequenced in 2001 and he’s now leading the next step—figuring out how to use that information. In his talk, Dr. Green outlined five active research areas that are taking us from what he called “helix to health:”

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When the disease is only half the battle…

by on February 17, 2012 at 10:33 am | 1 comment
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Jennifer Yashari, M.D., both a doctor and a patient, will represent the Neuromuscular Disease Foundation at Sanford-Burnham's annual Rare Disease Day Symposium on February 24.

Jennifer Yashari, M.D., both a doctor and a patient, will represent the Neuromuscular Disease Foundation at Sanford-Burnham's annual Rare Disease Day Symposium on February 24.

On February 24, we are holding our 3rd Annual Rare Disease Day Symposium in La Jolla, Calif. One of the speakers will be  Jennifer Yashari, M.D., representing the Neuromuscular Disease Foundation. Jennifer is not only a doctor, she’s also a patient. Read excerpts from her story below and join us for the main event next week. If you can’t make it, check back here the following week for video of each talk and more stories.

I grew up being told one thing over and over again by my parents, “All that matters is that you’re healthy. Nothing is as important as your health.” I never fully understood or appreciated the extent to which that was true until six years ago, when I became someone with a disease…

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Finding the cause of Liam’s metabolic disease

by on February 7, 2012 at 6:39 am | 0 Comments
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Liam

Liam

provided by Emory University

Sequencing a patient’s entire genome to discover the source of his or her disease is not routine – yet. But geneticists are getting close.

A case report, published February 2 in the American Journal of Human Genetics, shows how researchers can combine a simple blood test with an “executive summary” scan of the genome to diagnose a type of severe metabolic disease. In the study, researchers at Emory University School of Medicine and Sanford-Burnham used whole-exome sequencing to find the mutations causing a glycosylation disorder affecting Liam, a boy born in 2004.

Whole-exome sequencing reads only the parts of the human genome that encode proteins, leaving the other 99 percent of the genome unread. This method is cheaper and faster than whole-genome sequencing, but is still an efficient strategy for reading the parts of the genome scientists believe are the most important for diagnosing disease. It is estimated that most disease-causing mutations (around 85 percent) are found within the regions of the genome that encode proteins, the workhorse machinery of the cell. The report illustrates how whole-exome sequencing, which was first offered commercially for clinical diagnosis in 2011, is entering medical practice. Emory Genetics Laboratory is now gearing up to start offering whole-exome sequencing as a clinical diagnostic service.

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How antipsychotics cause side effects such as obesity and diabetes

by on January 31, 2012 at 3:15 pm | 3 Comments
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Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham

Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham

In 2008, roughly 14.3 million Americans were taking antipsychotics—typically prescribed for bipolar disorder, schizophrenia, or a number of other behavioral disorders—making them among the most prescribed drugs in the U.S. Almost all of these medications are known to cause metabolic side effects such as obesity and diabetes, leaving patients with a difficult choice between improving their mental health and damaging their physical health. In a paper published January 31 in the journal Molecular Psychiatry, researchers reveal how antipsychotic drugs interfere with normal metabolism by activating a protein called SMAD3, an important part of the transforming growth factor beta (TGFβ) pathway.

The TGFβ pathway is a cellular mechanism that regulates many biological processes, including cell growth, inflammation, and insulin signaling. In this study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not. What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.

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Third Annual Rare Disease Day Symposium: February 24

by on January 18, 2012 at 1:35 pm | 2 Comments
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Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation

Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation

What: Third Annual Sanford-Burnham Rare Disease Day Symposium: Identifying and Treating Genetic Diseases in Children
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif., Building 12 (map)
When: February 24, 2012 – registration opens at 8:00 a.m. PT, program begins at 9:00 a.m. PT
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute

Program and free registration: click here
Symposium flyer: download PDF
Can’t make it? Submit your genetic disease-related questions for panel discussion to Nick at nburchfi@sanfordburnham.org. The symposium will be recorded and available on Sanford-Burnham’s website shortly after the event.

Sanford-Burnham’s successful series of Rare Disease Day symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists. This year’s event, organized by Hudson Freeze, Ph.D., will focus on glycosylation-based disorders.

A few highlights:

  • Attendance by several children with Congenital Disorders of Glycosylation who are now benefiting from new therapies
  • Lunchtime panel discussion for patients and researchers
  • Presentation by patient advocacy group
  • Discussion of how one rare disorder relates to Parkinson’s disease

Video and media coverage of last year’s event are available here. For more information about Rare Disease Day USA (February 29, 2012), visit the National Organization for Rare Disorders.

A rare approach for a rare disease

by on November 23, 2011 at 12:29 pm | 2 Comments
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Mayor Hall of Bakersfield cuts the ribbon to open Salon Gianna. Beside him is Gianna, with Dr. Hudson Freeze and her mother, Natalie. On the right are Rocket’s parents, Mia and Taylor Williams, and Gianna’s father, David.

Mayor Hall of Bakersfield cuts the ribbon to open Salon Gianna. Beside him is Gianna, with Dr. Hudson Freeze and her mother, Natalie. On the right are Rocket’s parents, Mia and Taylor Williams, and Gianna’s father, David.

People who care about curing disease can be very creative in finding ways to raise money for research. Whether someone raises money and awareness by walking 60 miles, growing a mustache, or spending $50,000 on a pair of novelty sneakers, people’s passions fuel research funding.

The family that owns Salon Gianna, a beauty salon in Bakersfield, California, is on a mission to find a cure for Congenital Disorders of Glycosylation (CDG). All of their proceeds are earmarked for The Rocket Fund at Sanford-Burnham, which is overseen by Dr. Hudson Freeze. CDG is actually a group of more than 30 rare diseases caused by inherited defects in glycosylation, the process cells use to coat proteins with sugars. Young patients have a broad spectrum of clinical problems often including developmental delay, serious intestinal and liver complications, clotting defects, eye, skin, and other defects. Dr. Freeze’s lab seeks to treat and cure these diseases, often working closely with the families of affected children.

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Sisters in science

by on November 4, 2011 at 9:41 am | 0 Comments
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Dr. David Pearce, Vice President of Research at Sanford Health and Director of Sanford Children’s Health Research Center in Sioux Falls

Dr. David Pearce, Vice President of Research at Sanford Health and Director of Sanford Children’s Health Research Center in Sioux Falls

In late 2007, the Sanford Children’s Health Research Center was established at Sanford-Burnham’s La Jolla campus with a $20 million gift from South Dakota philanthropist T. Denny Sanford through Sanford Health. The gift was the foundation for a long-term partnership between Sanford Health, a large healthcare system based in South Dakota, and Sanford-Burnham. In addition to the center in La Jolla, in 2009 Sanford Health created a sister Children’s Health Research Center in Sioux Falls.

On October 27-28, researchers from both research centers gathered at Sanford-Burnham’s La Jolla campus to share new research directions and stimulate further collaboration at the fourth annual Sanford Children’s Health Research Center Scientific Symposium. Attendees heard overviews from the leaders of both Sanford-Burnham and Sanford Health and learned about Sanford Health’s new BioBank, a repository for patient samples that will help drive personalized medicine and provide fodder for population genomics studies. More than a dozen scientists presented their ongoing studies of embryonic development, type 1 diabetes, brain tumors, lung injury in newborns, and rare inherited conditions such as Batten disease. Hot topics also included stem cells and RNA biology.

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Save the Date: Third Annual Rare Disease Symposium

by on August 12, 2011 at 4:18 pm | 0 Comments
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Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation (CDG), hopes to see you at Sanford-Burnham's 3rd Annual Rare Disease Symposium on February 24, 2012.

Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation (CDG), hopes to see you at Sanford-Burnham's 3rd Annual Rare Disease Symposium on February 24, 2012.

Dr. Eric Green, keynote speaker (photo by Maggie Bartlett)

What: 3rd Annual Sanford-Burnham Rare Disease Symposium
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif.
When: February 24, 2012
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute (NHGRI) at the NIH

Sanford-Burnham’s successful series of Rare Disease symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists.

This year’s event, organized by Dr. Hudson Freeze, will focus on Glycosylation-Based Disorders: Discovery, Patients, and Progress Toward Treatments.

Save the date now. Program and registration information will be available soon. In the meantime, video and media coverage of last year’s event are available here.

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Science…under the Tuscan sun

by on July 21, 2011 at 2:24 pm | 0 Comments
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Harrison Ford plays a glycobiologist in the movie Extraordinary Measures.

In the movie Extraordinary Measures, Harrison Ford plays a glycobiologist.

 If brides and grooms can have destination weddings, then scientists should be able to have destination research conferences. These types of conferences are increasingly popular as opportunities for scientists to experience fun locales while also interacting and exchanging ideas with a relatively intimate group of expert colleagues. The Gordon Research Conferences have been trendsetters with this format since the 1930s, sponsoring scientific meetings on a variety of topics at sites within the U.S. Starting in 1990, Gordon Conferences have been held in more exotic foreign locations, including Italy, Switzerland, Japan, England, Hong Kong… and even Texas.

Earlier this summer, Dr. Hudson Freeze, program director in Sanford-Burnham’s Sanford Children’s Health Research Center, chaired the Gordon Conference on Glycobiology in Lucca, Italy. 170 glycobiologists from around the world gathered to hear about exciting new developments in the science of carbohydrates (sugar molecules) and the complex molecules like proteins and lipids whose properties are influenced by incorporation of carbohydrates. Once a rather understudied area of biology, glycobiology has been transformed by the realization that carbohydrates mediate many of the key molecular interactions that govern cellular function. Meeting topics included the effects of sugar modifications during development, the role of carbohydrates in normal adult physiology and the involvement of carbohydrates in tissue engineering and repair, including their importance in stem cell biology.

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My moment with Corinna

by on May 27, 2011 at 6:39 am | 0 Comments
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This video of three year-old Corinna is remarkable because it would seem so unremarkable if you didn’t know Corinna’s story—she looks just like any other kid. I had the pleasure of meeting this very special attendee at Sanford-Burnham’s 2nd Annual Rare Disease Day Symposium last February. Corinna was born with hypophosphatasia (HPP), a rare inherited disease that affects bone development, leaving her fragile and unable to walk. Lauren, Corinna’s mother, had brought her along to the symposium and was excited to meet the scientists studying HPP and hear about the latest research.

The family traveled from Philadelphia to be there that day – no small task, considering Corinna’s special needs and lack of mobility. I first talked to Lauren on the phone, helping her with directions from her hotel to the Sanford-Burnham campus. Then I waited for them outside and helped her get the stroller out of the taxi. I set it up while Lauren got Corinna out of the car. Corinna was blond, adorable, friendly—and just about the same size as my own daughter. My heart went out to them. I know how trying it can be to travel with a toddler, even under the best of circumstances.

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