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

Liu, Yi; Zhang, Yanqing; Zhao, Dongmei; Dong, Rui; Yang, Xiaomeng; Tammimies, Kristiina; Uddin, Mohammed; Scherer, Stephen W.; Gai, Zhongtao

doi:10.1002/ajmg.b.32306

Cited by 30 publications

(32 citation statements)

References 40 publications

(51 reference statements)

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“…Loci identified to be putative Ras/MAPK interaction partners influencing ASD risk in this way include or are adjacent to some already strong ASD candidate genes. GRM7 has been identified in rare, de novo CNV deletions[77,78] and single nucleotide mutations[79] in subjects with ASD and in a candidate gene SNP study. It encodes a metabotropic glutamate receptor critical for early development[80].…”

Section: Discussionmentioning

confidence: 99%

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

et al. 2017

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Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.

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Section: Discussionmentioning

confidence: 99%

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

et al. 2017

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“…[3][4][5] Emerging clinical evidence has associated the GRM7 locus with neurodevelopmental disorders. For example, homozygous point mutations in GRM7 have been reported in several patients with severe neurological diseases that are characterized by developmental delay and epilepsy, 6,7 while heterozygous mutations or deletions have been identified in patients with autism spectrum disorder (ASD) [8][9][10] and attention deficit hyperactivity disorder (ADHD). 11 Additionally, singlenucleotide polymorphisms have been associated with increased risk for ASD, ADHD and schizophrenia.…”

Section: Mglumentioning

confidence: 99%

Phenotypic profiling of mGlu₇ knockout mice reveals new implications for neurodevelopmental disorders

Fisher

Gould

Gogliotti

et al. 2020

Genes Brain and Behavior

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Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu7), a G protein‐coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu7 in the context of this specific disease class. Here, we show that the absence of mGlu7 in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu7 as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.

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“…More studies of patients with r(3) and 3p deletions are required to figure out the causes for the hearing loss of our patient. Some other genes have also been studied to be associated with growth retardation, neurological deficits, and muscle disease, such as CHL1 , CNTN6, CNTN4, TRNT1, CRBN,SUMF1,ITPR1,GRM7,SRGAP3,BRPF1,MTMR14, and so on [Fernandez et al, 2004;Gibbs et al, 2010;Huang et al, 2012;Ellery et al, 2014;Kashevarova et al, 2014;Kotecha et al, 2014;Tassano et al, 2014;Fabbri et al, 2015;Liu et al, 2015;Papuc et al, 2015;You et al, 2015], which are all deleted in our patient. As a result, it is highly likely that several genes interact to contribute to the phenotypes associated with r(3) and 3p deletions.…”

Section: B)mentioning

confidence: 74%

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

Zhang

Song²,

Zhang³

et al. 2016

Cytogenet Genome Res

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Ring chromosome 3, r(3), is an extremely rare cytogenetic abnormality with clinical heterogeneity and only 12 cases reported in the literature. Here, we report a 1-year-old girl presenting distinctive facial features, developmental delay, and congenital heart defects with r(3) and a ∼10-Mb deletion of chromosome 3pterp25.3 (61,891-9,979,408) involving 42 known genes which was detected using G-banding karyotyping and CytoScan 750K-Array. The breakpoints in r(3) were mapped at 3p25.3 and 3q29. We also analyzed the available information on the clinical features of the reported cases with r(3) and 3p deletion syndrome in order to provide more valuable information of genotype-phenotype correlations. To our knowledge, this is the largest detected fragment described in r(3) cases and the second r(3) study using whole-genome microarray.

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

Cited by 30 publications

References 40 publications

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Phenotypic profiling of mGlu₇ knockout mice reveals new implications for neurodevelopmental disorders

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

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

Cited by 30 publications

References 40 publications

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

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Phenotypic profiling of mGlu₇ knockout mice reveals new implications for neurodevelopmental disorders