A Rare De Novo Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation

Overview

Journal Biology (Basel)

Publisher MDPI

Specialty Biology

Date 2018 May 26

PMID 29794985

Citations 6

Authors

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

Affiliations

Soon will be listed here.

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.

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