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Archive - May 13, 2013

Sequencing Shows Spontaneous Mutations Are Major Cause of Congenital Heart Disease

Every year, thousands of babies are born with severely malformed hearts, disorders known collectively as congenital heart disease. Many of these defects can be repaired though surgery, but researchers don't understand what causes them or how to prevent them. New research shows that about 10 percent of these defects are caused by genetic mutations that are absent in the parents of affected children. Although genetic factors contribute to congenital heart disease, many children born with heart defects have healthy parents and siblings, suggesting that new mutations that arise spontaneously—known as de novo mutations—might contribute to the disease. "Until recently, we simply didn't have the technology to test for this possibility," says Howard Hughes Medical Institute (HHMI) investigator Dr. Richard Lifton. Dr. Lifton, who is at the Yale School of Medicine, together with Christine Seidman, an HHMI investigator at Brigham and Women's Hospital and colleagues at Columbia, Mt. Sinai, and the University of Pennsylvania, collaborated to study congenital heart disease through the National Heart, Lung, and Blood Institute's (NHLBI’s) Pediatric Cardiac Genomics Consortium. Using robust sequencing technologies developed in recent years, the researchers compared the protein-coding regions of the genomes of children with and without congenital heart disease and their parents, and found that new mutations could explain about 10 percent of severe cases. The results demonstrated that mutations in several hundred different genes contribute to this trait in different patients, but were concentrated in a pathway that regulates key developmental genes. These genes affect the epigenome, a system of chemical tags that modifies gene expression.

Renaissance in New Drugs for Rare Diseases Reported

Once famously described as "orphan diseases, too small to be noticed, too small to be funded" in the Hollywood film “Lorenzo's Oil,” rare diseases are getting unprecedented attention today among drug manufacturers, who are ramping up research efforts and marketing new medicines that promise fuller lives for children and other patients with these heartbreaking conditions. That's the conclusion of a major examination, published as the cover story of the May 13, 2013 issue of Chemical & Engineering News (C&EN), the weekly newsmagazine of the world's largest scientific society (the American Chemical Society--ACS), of the status of new drugs for the 7,000 conditions that affect 200,000 or fewer patients and fall into the "rare disease" category. The article was written by senior editor Lisa Jarvis after months of interviews with patients, parents, pharmaceutical industry officials, and others. C&EN reaches more than 138,000 scientists, policy-makers, educators, and others around the world. "For most of the last century, people afflicted by rare diseases — especially the parents and families of young children — shared the heartbreak of knowing that medicines to treat their loved ones were little more than a dream," says A. Maureen Rouhi, Ph.D., editor-in-chief of C&EN. "As our story documents in such compelling fashion, that situation is dramatically changing. Pharmaceutical companies are making unprecedented investments in medicines for these enigmatic conditions, popularized in films, and treatments for some are on the way." Jarvis describes how a combination of factors has coalesced to foster a renaissance in drug development for rare diseases.