Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder.

Abstract

GRM7, the gene encoding metabotropic glutamate receptor 7 (mGluR7), have been implicated in multiple neuropsychiatric disorders and shown to mediate excitatory synaptic neurotransmitter signaling and plasticity in the mammalian brain. Here we report a 303 kb de novo deletion at band 3p26.1, disrupting five coding exons of GRM7 in a proband with autism spectrum disorder, and hyperactivity. Our exon transcriptome-mutation contingency index method shows that three of the exons within the breakpoint boundaries are under purifying selection and highly expressed in prenatal brain regions. Based on our results and a thorough review of the literature, we propose that haploinsufficiency of the GRM7 product (mGluR7) contributes to autism spectrum disorders and hyperactivity phenotype as seen in the patient described here.

• Authors: Yi Liu, Yanqing Zhang, Dongmei Zhao, Rui Dong, Xiaomeng Yang, Kristiina Tammimies, Mohammed Uddin, Stephen W Scherer, Zhongtao Gai
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 168B Issue 4 Pg. 258-64 (Jun 2015) ISSN: 1552-485X [Electronic] United States
• PMID: 25921429 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 7

Topics

• Autism Spectrum Disorder (genetics)
• Child
• Child, Preschool
• DNA Copy Number Variations (genetics)
• Exons (genetics)
• Gene Deletion
• Genetic Predisposition to Disease
• Humans
• Male
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide (genetics)
• Receptors, Metabotropic Glutamate (genetics)