PMID- 29794985 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 7 IP - 2 DP - 2018 May 24 TI - A Rare De Novo RAI1 Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation. LID - 10.3390/biology7020031 [doi] LID - 31 AB - 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. FAU - Abad, Clemer AU - Abad C AD - John P. Hussman Institute for Human Genomics, University of Miami, FL 33136, USA. cabad@med.miami.edu. FAU - Cook, Melissa M AU - Cook MM AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. mcook@ggc.org. FAU - Cao, Lei AU - Cao L AD - John P. Hussman Institute for Human Genomics, University of Miami, FL 33136, USA. LCao@med.miami.edu. FAU - Jones, Julie R AU - Jones JR AD - Molecular Diagnostic Laboratory, Greenwood Genetic Center, Greenwood, SC 29646, USA. juliejones@ggc.org. FAU - Rao, Nalini R AU - Rao NR AD - John P. Hussman Institute for Human Genomics, University of Miami, FL 33136, USA. n.rao@miami.edu. FAU - Dukes-Rimsky, Lynn AU - Dukes-Rimsky L AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. ldrimsky@ggc.org. FAU - Pauly, Rini AU - Pauly R AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. rpauly@ggc.org. FAU - Skinner, Cindy AU - Skinner C AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. cds11251977@gmail.com. FAU - Wang, Yunsheng AU - Wang Y AD - School of Computing, Clemson University, Clemson, SC 29634, USA. yunshew@g.clemson.edu. FAU - Luo, Feng AU - Luo F AD - School of Computing, Clemson University, Clemson, SC 29634, USA. luofeng@clemson.edu. FAU - Stevenson, Roger E AU - Stevenson RE AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. res@ggc.org. FAU - Walz, Katherina AU - Walz K AD - John P. Hussman Institute for Human Genomics, University of Miami, FL 33136, USA. KWalz@med.miami.edu. AD - Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL 33136, USA. KWalz@med.miami.edu. FAU - Srivastava, Anand K AU - Srivastava AK AD - J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. anand@ggc.org. AD - Department of Genetics and Biochemsitry, Clemson University, Clemson, SC 29634, USA. anand@ggc.org. LA - eng GR - R01 HD039331/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20180524 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC6023015 OTO - NOTNLM OT - RAI1 OT - Smith-Magenis syndrome OT - autism spectrum disorder OT - mutation OT - neurodevelopmental disorder COIS- The Molecular and Cytogenetic Diagnostic Laboratories at the Greenwood Genetic Center receive revenue for Next Generation Sequencing panels, microarrays, and various other genetic tests. EDAT- 2018/05/26 06:00 MHDA- 2018/05/26 06:01 PMCR- 2018/06/01 CRDT- 2018/05/26 06:00 PHST- 2018/04/17 00:00 [received] PHST- 2018/05/20 00:00 [revised] PHST- 2018/05/21 00:00 [accepted] PHST- 2018/05/26 06:00 [entrez] PHST- 2018/05/26 06:00 [pubmed] PHST- 2018/05/26 06:01 [medline] PHST- 2018/06/01 00:00 [pmc-release] AID - biology7020031 [pii] AID - biology-07-00031 [pii] AID - 10.3390/biology7020031 [doi] PST - epublish SO - Biology (Basel). 2018 May 24;7(2):31. doi: 10.3390/biology7020031.