Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis

Roberta L. Beauchamp, Ashleigh Banwell, Patrick McNamara, Matthew Jacobsen, Erica Higgins, Hope Northrup, Priscilla Short, Katherine Sims, Laurie Ozelius, Vijaya Ramesh

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Tuberous sclerosis complex (TSC) is a dominantly inherited multisystem disorder resulting in the development of hamartomatous growths in many organs. Genetic heterogeneity has been demonstrated linking the familial cases to either TSC1 at 9q34.3, or TSC2 at 16p13.3. About two-thirds of the TSC cases are sporadic and appear to represent new mutations. While both genes are thought to account for all familial cases, with each representing approximately 50% of the mutations, the proportion of sporadic cases with mutations in TSC1 and TSC2 is yet to be determined. We have examined the entire coding sequence of the TSC2 gene in 20 familial and 20 sporadic cases and identified a total of twenty-one mutations representing 50% and 55% of familial and sporadic cases respectively. Our rate of mutation detection is significantly higher than other published reports. Twenty out of 21 mutations are novel and include 6 missense, 6 nonsense, 5 frame, shifts, 2 splice alterations, a 34 bp deletion resulting in abnormal splicing, and an 18 bp deletion which maintains the reading frame. The mutations are distributed throughout the coding sequence with no specific hot spots. There is no apparent correlation between mutation type and clinical severity of the disease. Our results document that at least 50% of sporadic cases arise from mutations in the TSC2 gene. The location of the mutations described here, particularly the missense events, should be valuable for further functional analysis of this tumor suppressor protein.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalHuman mutation
Issue number6
StatePublished - 1998
Externally publishedYes


  • Mutations
  • SSCP
  • TSC2
  • Tuberin
  • Tuberous sclerosis complex


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