NICHD Funded Researchers Discover Gene for Cornelia De Lange Syndrome

Discovery May Lead to Prenatal Test For Debilitating Disorder

A team of researchers has discovered a gene for Cornelia de Lange Syndrome, a disorder consisting of mental retardation, heart defects and a number of physical abnormalities. The researchers were funded by the National Institute of Child Health and Human Development, one of the National Institutes of Health.

The researchers expect the discovery to speed the development of a prenatal genetic test for the syndrome. A similar test will also be developed to diagnose Cornelia de Lange Syndrome in young children suspected of having the disorder.

The study was published on May 16 in the online edition of Nature Genetics.

"The discovery of the gene for Cornelia de Lange Syndrome also offers the chance to learn more about the disorder, and perhaps to develop new treatments for it," said Duane Alexander, M.D., Director of the NICHD.

The first author of the study was Ian Krantz, M.D., of the University of Pennsylvania in Philadelphia and The Children's Hospital of Philadelphia.

Named for the Dutch physician who first described it in 1933, Cornelia de Lange Syndrome involves a complex of symptoms. These include mental retardation, self-injurious behavior, impaired growth, heart defects, hearing loss, and abnormalities of the fingers and hands. Individuals with Cornelia de Lange Syndrome also have distinctive facial features, such as thin eyebrows that meet in the middle of the forehead, long eyelashes, thin, down-turned lips, and excessive body hair. According to the study authors, Cornelia De Lange Syndrome occurs in one of every 10,000 individuals.

In a study involving 5 hospitals and 8 universities, the researchers analyzed the genes of 12 families that each has more than one member with Cornelia de Lange Syndrome. They discovered that the gene for the disorder resides on the 5th chromosome. They named the gene, NIPBL, which stands for "Nipped B-like." The gene is named after its counterpart in fruit flies, "Nipped B." Fruit flies having the gene have abnormal wings, which look like they have a small bite taken out of them. The discovery of the Nipped B gene was funded in part by the National Institute of General Medical Sciences, also at the NIH.

In both fruit flies and human beings, the gene appears to be involved in the very early stages of embryonic development, Dr. Krantz said. NIPBL contains the information needed to make a protein that helps to switch on a number of other genes.

Other institutions taking part in the study were: The Geneva University Hospital in Geneva, Switzerland; the University of Nevada School of Medicine in Las Vegas; the University Medical Center in Hamilton, Ontario; Michigan State University in East Lansing; the University of Utah Health Sciences Center; the University of California in Irvine; Nemours Children's Clinic in Wilmington, Delaware; the University of Genoa, Italy; and Drexel University School of Medicine in Philadelphia.


The NICHD is part of the National Institutes of Health (NIH), the biomedical research arm of the federal government. NIH is an agency of the U.S. Department of Health and Human Services. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site,, or from the NICHD Information Resource Center, 1-800-370-2943; e-mail

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