Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States

Kit Sing Au, Aimee T. Williams, E. Steve Roach, Lori Batchelor, Steven P. Sparagana, Mauricio R. Delgado, James W. Wheless, James E. Baumgartner, Benjamin B. Roa, Carolyn M. Wilson, Teresa K. Smith-Knuppel, Min Yuen C Cheung, Vicky H. Whittemore, Terri M. King, Hope Northrup

Research output: Contribution to journalArticle

233 Scopus citations

Abstract

Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Correlating genotypes with phenotypes should facilitate the disease management of tuberous sclerosis complex.

Original languageEnglish (US)
Pages (from-to)88-100
Number of pages13
JournalGenetics in Medicine
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Genotype-phenotype correlation
  • Meta-analysis
  • Mutation screening
  • Tuberous sclerosis complex
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Genetics(clinical)

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    Au, K. S., Williams, A. T., Roach, E. S., Batchelor, L., Sparagana, S. P., Delgado, M. R., Wheless, J. W., Baumgartner, J. E., Roa, B. B., Wilson, C. M., Smith-Knuppel, T. K., Cheung, M. Y. C., Whittemore, V. H., King, T. M., & Northrup, H. (2007). Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genetics in Medicine, 9(2), 88-100. https://doi.org/10.1097/GIM.0b013e31803068c7