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A Rare De Novo Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation. Biology (Basel) 2018 May 24;7(2) PMID: 29794985 PMCID: PMC6023015

Pubmed ID

29794985

Abstract

Deletions and mutations involving the Retinoic Acid Induced 1 () 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 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 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities.

Author List

Abad C, Cook MM, Cao L, Jones JR, Rao NR, Dukes-Rimsky L, Pauly R, Skinner C, Wang Y, Luo F, Stevenson RE, Walz K, Srivastava AK

Author

Test M. User in the Anesthesiology department at Medical College of Wisconsin




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