Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder.
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.
Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Yi
Y
Liu
Pediatric Health Care Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Yanqing
Y
Zhang
Pediatric Health Care Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Dongmei
D
Zhao
Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Rui
R
Dong
Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Xiaomeng
X
Yang
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.|The Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Kristiina
K
Tammimies
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.
Mohammed
M
Uddin
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.|McLaughlin Centre and Department of Molecular Genetics, University ofToronto, Toronto, Canada.
Stephen W
SW
Scherer
Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.|Pediatric Health Care Institute, Qilu Children's Hospital of Shandong University, Ji'nan, China.
Zhongtao
Z
Gai
D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*
D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7
autism spectrum disorders (ASDs); metabotropic glutamate receptor 7 gene (GRM7); neuropsychiatric disorders