Finding may aid diagnosis of learning disabilities linked to brain tumor syndrome​​

July 22, 2015 by Michael C. Purdy, Washington University School of Medicine in St. Louis

New insight into one of the most common inherited causes of brain tumors may help physicians diagnose and treat the learning disabilities that often accompany the condition.

Studying patients' skin samples and novel strains of , researchers at Washington University School of Medicine in St. Louis found that that cause neurofibromatosis 1 (NF1) can have varying effects on levels of dopamine, a signaling molecule in the brain associated with learning and attention. Some mutations dramatically decreased , while others had little to no effect on dopamine.

"The surprising findings, made using patient-derived skin cells, have changed the way we think about how NF1 mutations cause learning problems," said senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology. "This may help us identify which patients are most likely to benefit from approved medications that increase dopamine levels in the brain, such as Ritalin."

The findings are available online in Human Molecular Genetics.

Scientists estimate that NF1 affects one in every 2,500 people. Although rarely fatal, it is among the most common inherited pediatric brain cancer syndromes. Over half of all NF1 patients also have significant learning and attention problems.

NF1 is caused by mutations in the gene that makes a protein called neurofibromin. In studies using brain generated from NF1 patient skin cell-derived stem cells, Gutmann and his colleagues found that different NF1 gene mutations caused these nerve cells to produce either slightly reduced levels of neurofibromin or dramatically lower neurofibromin levels. Importantly, the amount of neurofibromin correlated with the levels of dopamine.

"Although the specific NF1-causing mutations varied among the patients, there was no middle ground—they either had near-normal levels of dopamine or more than 75 percent reductions in dopamine," Gutmann said.

The scientists then generated mice to mimic these differences in neurofibromin levels. One group had dramatically reduced levels of the protein in dopamine-producing nerve cells, while the other had only slightly reduced levels.

Testing showed that only mice with the lowest neurofibromin levels had memory problems. In contrast, those with more mild decreases in neurofibromin performed as well as control mice.

The mice with the lowest levels of neurofibromin also had the greatest reductions in compared with the mice with more neurofibromin.

"We were surprised to find that not all NF1 mutations have the same effects on the ," Gutmann said. "We're working with colleagues to see if we can develop a blood test to help us predict learning disabilities in patients with NF1. We hope that this will lead to improved ways to diagnose and treat children with these cognitive challenges."

Explore further: Many causes for learning lags in tumor disorder

More information: "Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning." Human Molecular Genetics, June 15, 2015 DOI: 10.1093/hmg/ddv103

Related Stories

Many causes for learning lags in tumor disorder

December 21, 2012
(Medical Xpress)—The causes of learning problems associated with an inherited brain tumor disorder are much more complex than scientists had anticipated, researchers at Washington University School of Medicine in St. Louis ...

Researchers identify therapeutic strategy that may treat childhood neurological disorder

December 15, 2014
UT Southwestern Medical Center researchers have identified a possible therapy to treat neurofibromatosis type 1 or NF1, a childhood neurological disease characterized by learning deficits and autism that is caused by inherited ...

Gender influences symptoms of genetic disorder

February 7, 2014
(Medical Xpress)—A genetic disorder that affects about 1 in every 2,500 births can cause a bewildering array of clinical problems, including brain tumors, impaired vision, learning disabilities, behavioral problems, heart ...

Brain scans reveal drugs' effects on attention

October 14, 2011
(Medical Xpress) -- Scientists have developed a way to evaluate new treatments for some forms of attention deficit disorder.

Recommended for you

New neurons in the adult brain are involved in sensory learning

February 23, 2018
Although we have known for several years that the adult brain can produce new neurons, many questions about the properties conferred by these adult-born neurons were left unanswered. What advantages could they offer that ...

Neuroscientists discover a brain signal that indicates whether speech has been understood

February 22, 2018
Neuroscientists from Trinity College Dublin and the University of Rochester have identified a specific brain signal associated with the conversion of speech into understanding. The signal is present when the listener has ...

Study in mice suggests personalized stem cell treatment may offer relief for multiple sclerosis

February 22, 2018
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis ...

Nolan film 'Memento' reveals how the brain remembers and interprets events from clues

February 22, 2018
Key repeating moments in the film give viewers the information they need to understand the storyline. The scenes cause identical reactions in the viewer's brain. The results deepen our understanding of how the brain functions, ...

Biomarker, clues to possible therapy found in novel childhood neurogenetic disease

February 22, 2018
Researchers studying a rare genetic disorder that causes severe, progressive neurological problems in childhood have discovered insights into biological mechanisms that drive the disease, along with early clues that an amino ...

A look at the space between mouse brain cells

February 22, 2018
Between the brain's neurons and glial cells is a critical but understudied structure that's been called neuroscience's final frontier: the extracellular space. With a new imaging paradigm, scientists can now see into and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.