The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis

G. D. Strizheva, T. Carsillo, W. D. Kruger, E. J. Sullivan, J. H. Ryu, E. P. Henske

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Lymphangiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex (TSC). Because only a minority of women with TSC develops symptomatic LAM, we hypothesized that a relationship might exist between the type of germline TSC1 or TSC2 gene mutation and the risk of developing LAM. We examined all 41 exons of the TSC2 gene and 21 coding exons of the TSC1 gene for mutations in a group of 14 women with both TSC and LAM using single-strand conformation polymorphism analysis. Seven mutations were found in TSC2 and one in TSC1. Of the seven patients with TSC2 mutations, two had the same in-frame exon 40 deletion and one had an exon 41 missense change. We conclude that germline mutations in the extreme carboxy-terminus of tuberin can result in LAM. Further studies will be required to determine whether mutations in exons 40 and 41 are associated with an increased incidence and/or severity of LAM in women with TSC.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume163
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Exons/genetics
  • Female
  • Genes, Tumor Suppressor/genetics
  • Humans
  • Lymphangioleiomyomatosis/complications
  • Mutation
  • Proteins/genetics
  • Repressor Proteins/genetics
  • Sequence Analysis, DNA
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tuberous Sclerosis/complications
  • Tumor Suppressor Proteins

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