Molecular genetic basis of tuberous sclerosis complex: from bench to bedside.
Tuberous sclerosis complex is an autosomal dominant disease of benign tumors occurring in multiple organ systems of the body. Either of two genes, TSC1 or TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype. The protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and tuberin (TSC2), have been discovered to play important roles in several cell-signaling pathways. Knowledge regarding the function of the tuberin-hamartin complex has led to therapeutic intervention trials. Numerous pathogenic mutations have been elucidated in individuals affected with tuberous sclerosis complex. Information on the type and distribution of nearly 1000 mutations in the two genes is discussed. Mosaicism for tuberous sclerosis complex mutations has been documented, complicating provision of genetic counseling to families. Emerging genotype-phenotype correlations should provide guidance for better medical care of individuals with tuberous sclerosis complex.
Au
Kit-Sing
KS
Department of Pediatrics, Division of Medical Genetics, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
Williams
Aimee T
AT
Gambello
Michael J
MJ
Northrup
Hope
H
D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D002648:Child; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics* / Q000494:pharmacology; D015398:Signal Transduction; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins