title: Analysis of TSC2 stop codon variants found in tuberous sclerosis patients.
abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.
authors.affiliation: Department of Clinical Genetics, Erasmus University and Dijkzigt Academic Hospital, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Goedbloed
authors.forename: M
authors.initials: M
authors.lastname: Nellist
authors.forename: B
authors.initials: B
authors.lastname: Verhaaf
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: D
authors.initials: D
authors.lastname: Lindhout
authors.forename: L
authors.initials: L
authors.lastname: Sunde
authors.forename: S
authors.initials: S
authors.lastname: Verhoef
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
mesh_terms: D000818:Animals; D019556:COS Cells; D018388:Codon, Terminator / Q000235:genetics*; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques
chemical_list: D018388:Codon, Terminator; 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