Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex

Eur J Hum Genet. 2005 Jun;13(6):731-41. doi: 10.1038/sj.ejhg.5201402.


Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in multiple organs and tissues. TSC is caused by mutations in either the TSC1 or TSC2 gene. We searched for mutations in both genes in a cohort of 490 patients diagnosed with or suspected of having TSC using a combination of denaturing gradient gel electrophoresis, single-strand conformational polymorphism, direct sequencing, fluorescent in situ hybridisation and Southern blotting. We identified pathogenic mutations in 362 patients, a mutation detection rate of 74%. Of these 362 patients, 276 had a definite clinical diagnosis of TSC and in these patients 235 mutations were identified, a mutation detection rate of 85%. The ratio of TSC2:TSC1 mutations was 3.4:1. In our cohort, both TSC1 mutations and mutations in familial TSC2 cases were associated with phenotypes less severe than de novo TSC2 mutations. Interestingly, consistent with other studies, the phenotypes of the patients in which no mutation was identified were, overall, less severe than those of patients with either a known TSC1 or TSC2 mutation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blotting, Southern
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis / methods*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Genotype
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Repressor Proteins / genetics*
  • Severity of Illness Index
  • Tuberous Sclerosis / genetics*
  • Tuberous Sclerosis / pathology
  • Tuberous Sclerosis / physiopathology
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*


  • Repressor Proteins
  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins