A rare de novo RAI1 gene mutation affecting BDNF-enhancer-driven transcription activity associated with autism and atypical smith-magenis syndrome presentation

Clemer Abad, Melissa M. Cook, Lei Cao, Julie R. Jones, Nalini R. Rao, Lynn Dukes-Rimsky, Rini Pauly, Cindy Skinner, Yunsheng Wang, Feng Luo, Roger E. Stevenson, Katherina Walz, Anand K. Srivastava

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Deletions and mutations involving the Retinoic Acid Induced 1 (RAI1) gene at 17p11.2 cause Smith-Magenis syndrome (SMS). Here we report a patient with autism as the main clinical presentation, with some SMS-like features and a rare de novo RAI1 gene mutation, c.3440G > A (p.R1147Q). We functionally characterized the RAI1 p.R1147Q mutant protein. The mutation, located near the nuclear localization signal, had no effect on the subcellular localization of the mutant protein. However, similar to previously reported RAI1 missense mutations in SMS patients, the RAI1 p.R1147Q mutant protein showed a significant deficiency in activating in vivo transcription of a reporter gene driven by a BDNF (brain-derived neurotrophic factor) intronic enhancer. In addition, expression of other genes associated with neurobehavioral abnormalities and/or neurodevelopmental disorders were found to be altered in this patient. These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities.

Original languageEnglish (US)
Article number31
JournalBiology
Volume7
Issue number2
DOIs
StatePublished - Jun 2018

Keywords

  • Autism spectrum disorder
  • Mutation
  • Neurodevelopmental disorder
  • RAI1
  • Smith-Magenis syndrome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Abad, C., Cook, M. M., Cao, L., Jones, J. R., Rao, N. R., Dukes-Rimsky, L., Pauly, R., Skinner, C., Wang, Y., Luo, F., Stevenson, R. E., Walz, K., & Srivastava, A. K. (2018). A rare de novo RAI1 gene mutation affecting BDNF-enhancer-driven transcription activity associated with autism and atypical smith-magenis syndrome presentation. Biology, 7(2), [31]. https://doi.org/10.3390/biology7020031