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

Am J Med Genet B Neuropsychiatr Genet. 2015 Jun;168B(4):258-64. doi: 10.1002/ajmg.b.32306. Epub 2015 Apr 29.

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.

Keywords: autism spectrum disorders (ASDs); metabotropic glutamate receptor 7 gene (GRM7); neuropsychiatric disorders.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 7