Dataset Information

Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies CAPG as a Functionally Relevant Candidate Gene.

ABSTRACT: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with high heritability, although their underlying genetic factors are still largely unknown. Here we present a comprehensive genetic characterization of two ASD siblings from Sardinia by genome-wide copy number variation analysis and whole exome sequencing (WES), to identify novel genetic alterations associated with this disorder. Single nucleotide polymorphism (SNP) array data revealed a rare microdeletion involving CAPG, ELMOD3, and SH2D6 genes, in both siblings. CAPG encodes for a postsynaptic density (PSD) protein known to regulate spine morphogenesis and synaptic formation. The reduced CAPG mRNA and protein expression levels in ASD patients, in the presence of hemizygosity or a particular genetic and/or epigenetic background, highlighted the functional relevance of CAPG as a candidate gene for ASD. WES analysis led to the identification in both affected siblings of a rare frameshift mutation in VDAC3, a gene intolerant to loss of function mutation, encoding for a voltage-dependent anion channel localized on PSD. Moreover, four missense damaging variants were identified in genes intolerant to loss of function variation encoding for PSD proteins: PLXNA2, KCTD16, ARHGAP21, and SLC4A1. This study identifies CAPG and VDAC3 as candidate genes and provides additional support for genes encoding PSD proteins in ASD susceptibility.

SUBMITTER: Bacchelli E

PROVIDER: S-EPMC6406497 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies <i>CAPG</i> as a Functionally Relevant Candidate Gene.

Bacchelli Elena E Loi Eleonora E Cameli Cinzia C Moi Loredana L Vega-Benedetti Ana Florencia AF Blois Sylvain S Fadda Antonio A Bonora Elena E Mattu Sandra S Fadda Roberta R Chessa Rita R Maestrini Elena E Doneddu Giuseppe G Zavattari Patrizia P

Journal of clinical medicine 20190207 2

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with high heritability, although their underlying genetic factors are still largely unknown. Here we present a comprehensive genetic characterization of two ASD siblings from Sardinia by genome-wide copy number variation analysis and whole exome sequencing (WES), to identify novel genetic alterations associated with this disorder. Single nucleotide polymorphism (SNP) array data revealed a rare microdeletion involving <i ...[more]

PMID: 30736458

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Dataset Information

Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies CAPG as a Functionally Relevant Candidate Gene.

Publications

Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies <i>CAPG</i> as a Functionally Relevant Candidate Gene.

Similar Datasets

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