A medical mystery for children with an unusual array of symptoms has been unlocked by researchers funded in part by the March of Dimes, who have identified a genetic mutation underlying a new form of muscular dystrophy (MD). The work was published today in the American Journal of Human Genetics.
M. Chiara Manzini, PhD, of The George Washington University and Yalda Jamshidi, PhD, of St. George’s University of London worked with an international group of colleagues to demonstrate that mutations in the INPP5K gene are responsible for a unique form of MD that has puzzled doctors because its features – including short stature, cataracts, and intellectual disability – overlap with other disorders.
“Families and physicians have been searching for the origins of this rare disorder for years,” Dr. Manzini says. “Children with a similar combination of symptoms had been described in the medical literature before, but it was unclear whether or not it was a new disease. Now we know it’s a variant of MD that affects other organs.”
“This is a great example of collaborative, innovative genetic research that has an immediate benefit to babies and their families,” says Joe Leigh Simpson, MD, senior vice president for Research and Global Programs at the March of Dimes. “Studying rare disorders can also teach us more about common conditions that affect millions of people in the United States and around the world.”
The far-flung research team used web-based technology that allowed them to compare the particular gene they were studying with a large genetic database, and find and enroll more patients in their study. In the process, they discovered another research group in Germany was also working on the INPP5K gene (see this issue of the journal for the other paper).
Dr. Jamshidi calls INPP5K “a major player” in muscle and brain development that is fascinating to study because it functions differently from other known MD genes inside cells to regulate signaling and response. She says the next step for the research team is to learn more about why INPP5K functions as it does.
Identifying a target MD gene gives a boost to both patients and other scientists, the researchers note. The information gives a focus to investigators seeking new treatments for MD, and gives hope to families that such treatments will become available in the foreseeable future. Patients with MD can benefit from genetic screening and counseling, and obtaining a precise diagnosis can reduce uncertainly for their families. In addition, knowing their child’s disorder can help families understand which medical specialists to consult for their child’s care; while caring for more affected children helps doctors better understand the disease, its variability and progression.
Muscular dystrophy is a disorder in which the muscles progressively degenerate over time. More than 250,000 Americans are affected by the known forms of MD and other related neuromuscular disorders. Among this group are childhood conditions such as Duchenne and Becker muscular dystrophies and congenital muscular dystrophy. MD can occur due to inheriting a defective gene from one's parents, which affects muscle development and function.
“Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy” by Daniel P.S. Osborn et al. appears today online in the American Journal of Human Genetics and will be published in the March 2 print edition. It was supported by the March of Dimes and other organizations including the Muscular Dystrophy Association.