Spotlight on Research for 2006

August 2006 (historical)

Genetic Findings Lead to Prenatal Testing and Counseling for Blistering Skin Disease

An estimated 20,000 to 40,000 Americans suffer from epidermolysis bullosa (EB), a collection of inherited skin diseases characterized by recurring skin blistering, often in response to minor trauma. In severe forms of the disease, patients may experience damage to other tissues and organs - including the eyes, esophagus, gastrointestinal and urinary tracts, and muscles - which can be fatal.

The most common form of EB, epidermolysis bullosa simplex (EBS), is the least severe, yet can still cause skin blistering beginning at birth when the baby’s fragile skin is subjected to the trauma of delivery. Now, research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) suggests that the risks to these children may be minimized with prenatal testing that enables doctors and prospective parents to diagnose unborn babies with EBS and take special precautions at delivery.

Prenatal diagnosis of EBS relies on finding of mutations in genes for keratin (a family of proteins that help maintain cell shape and strength) including keratin 5 (KRT5) and keratin 14 (KRT14), through chorionic villus sampling (CVS), says Jouni Uitto, M.D., Ph.D., professor and chair of the department of dermatology and cutaneous biology and professor of biochemistry and molecular biology at Philadelphia's Thomas Jefferson University. CVS is a test performed on a small sample of the placenta as early as the 10th week of pregnancy.

EBS is in most cases an autosomal dominant disease, which means that if one parent has the disease, a child has a 50/50 chance of having it as well. But Uitto’s research shows that the disease can occur more commonly than expected among children in whom neither parent has the disease. In those cases, the cause is a de novo mutation in the KRT5 or KRT14 gene in one parent's sperm or egg cells. Parents who have had one child as a result of such a mutation have been estimated to have somewhere between a one and five percent chance of having another child with the disease, making them candidates for prenatal testing and counseling, says Dr. Uitto.

In a study published in the Journal of Investigative Dermatology, Dr. Uitto and his colleagues analyzed eight pregnancies in eight families affected with EBS. In three families, one of the parents was affected. Two of the three pregnancies were positive, showing recurrence of the dominant paternally inherited mutation. In the other five families, the parents were not affected, but had a previous child with a de novo mutation. All five of those pregnancies were normal. "Clearly, these families did not request prenatal testing for termination purposes, but primarily to know if the child is affected so they can prepare for delivery in an appropriate hospital setting with expertise on this disease," says Dr. Uitto. The researchers’ next goal is to develop a test by which the disease can be detected noninvasively through a blood test that detects fetal DNA in the mother’s bloodstream, possibly as early as the 5th week of gestation.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at

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Pfendner EG, Sadowski SG, Uitto J. Epidermolysis Bullosa Simplex: Recurrent and de novo mutations in the KRT5 and KRT14 genes, phenotype/genotype correlations, and implications for genetic counseling and prenatal diagnosis. J Invest Dermatol 2005;125:239-243.