NSD1 analysis for Sotos syndrome: Insights and perspectives from the clinical laboratory

Darrel J. Waggoner, Gordana Raca, Katherine Welch, Melissa Dempsey, Ethan Anderes, Irina Ostrovnaya, Asem Alkhateeb, Junichi Kamimura, Naomichi Matsumoto, G. Bradley Schaeffer, Christa Lese Martin, Soma Das

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Purpose: Sotos syndrome is a genetic disorder characterized primarily by overgrowth, developmental delay, and a characteristic facial gestalt. Defects in the NSD1 gene are present in approximately 80% of patients with Sotos syndrome. The goal of this study was to determine the incidence of NSD1 abnormalities in patients referred to a clinical laboratory for testing and to identify clinical criteria that distinguish between patients with and without NSD1 abnormalities. Methods: Deletion or mutation analysis of the NSD1 gene was performed on 435 patients referred to our clinical genetics laboratory. Detailed clinical information was obtained on 86 patients with and without NSD1 abnormalities, and a clinical checklist was developed to help distinguish between these two groups of patients. Results: Abnormalities of the NSD1 gene were identified in 55 patients, including 9 deletions and 46 mutations. Thus, in the clinical laboratory setting, deletions were found in 2% and mutations in 21% of samples analyzed, because not all patients had both tests. Thirty-three previously unreported mutations in the NSD1 gene were identified. Clinical features typically associated with Sotos syndrome were not found to be significantly different between individuals with and without NSD1 abnormalities. The clinical checklist developed included poor feeding, increased body mass index, and enlarged cerebral ventricles, in addition to the typical clinical features of Sotos syndrome, and was able to distinguish between the two groups with 80% sensitivity and 70% specificity. Conclusions: The dramatic decrease in the frequency of finding NSD1 abnormalities in the clinical laboratory is likely because of the heterogeneity of the patient population. Our experience from a diagnostic laboratory can help guide clinicians in deciding for whom NSD1 genetic analysis is indicated.

Original languageEnglish
Pages (from-to)524-533
Number of pages10
JournalGenetics in Medicine
Issue number8
Publication statusPublished - Oct 2005
Externally publishedYes



  • Laboratory testing
  • NSD1
  • Sotos syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Waggoner, D. J., Raca, G., Welch, K., Dempsey, M., Anderes, E., Ostrovnaya, I., Alkhateeb, A., Kamimura, J., Matsumoto, N., Schaeffer, G. B., Martin, C. L., & Das, S. (2005). NSD1 analysis for Sotos syndrome: Insights and perspectives from the clinical laboratory. Genetics in Medicine, 7(8), 524-533. https://doi.org/10.1097/01.GIM.0000178503.15559.d3