Scientists have identified the second of two genes that cause tuberous sclerosis complex (TSC), a relatively common developmental disorder characterized by a number of abnormalities, including seizures, benign tumors in several organs, and variable emotional and cognitive disabilities. The discovery, to be reported in the August 8, 1997, issue of Science* by David Kwiatkowski, M.D., Ph.D., and colleagues at Brigham and Women's Hospital in Boston, was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Human Genome Research Institute (NHGRI), both components of the National Institutes of Health.
Investigators located the TSC1 gene on chromosome 9. The gene makes a protein called hamartin, named after hamartomas, a type of tumor common to TSC and comprised of multiple cell types. Affected individuals have a mutation in either the TSC1 gene or the TSC2 gene. The TSC2 gene, which codes for a protein called tuberin, is located on chromosome 16 and was identified in 1993 by a European consortium of investigators. Both the TSC1 and TSC2 genes are thought to function as tumor suppressor genes and join more than a dozen other such genes that play an important role in the control of cell growth. In their normal form, tumor suppressor genes keep cells from multiplying unchecked in the body and prevent tumor development.
TSC occurs in one in 6,000 live births and affects a total of 40,000 Americans
and 1,000,000 people worldwide. It is called a complex because of the wide
range of clinical manifestations. Clinical signs may be subtle and, as a
result, TSC can go unrecognized or misdiagnosed for many years. Although in
some individuals it may take considerable time before symptoms develop, TSC is
known primarily as a childhood disorder. Generally speaking, the clinical
manifestations of TSC are the same for both genes. Seizures are the most co
Contact: Stephanie Clipper
NIH/National Institute of Neurological Disorders and Stroke