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Cell Syst 2021 Nov 17;1211:1094-1107.e6. doi: 10.1016/j.cels.2021.07.009.
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A convergent molecular network underlying autism and congenital heart disease.

Rosenthal SB , Willsey HR , Xu Y , Mei Y , Dea J , Wang S , Curtis C , Sempou E , Khokha MK , Chi NC , Willsey AJ , Fisch KM , Ideker T .

Patients with neurodevelopmental disorders, including autism, have an elevated incidence of congenital heart disease, but the extent to which these conditions share molecular mechanisms remains unknown. Here, we use network genetics to identify a convergent molecular network underlying autism and congenital heart disease. This network is impacted by damaging genetic variants from both disorders in multiple independent cohorts of patients, pinpointing 101 genes with shared genetic risk. Network analysis also implicates risk genes for each disorder separately, including 27 previously unidentified genes for autism and 46 for congenital heart disease. For 7 genes with shared risk, we create engineered disruptions in Xenopus tropicalis, confirming both heart and brain developmental abnormalities. The network includes a family of ion channels, such as the sodium transporter SCN2A, linking these functions to early heart and brain development. This study provides a road map for identifying risk genes and pathways involved in co-morbid conditions.

PubMed ID: 34411509
PMC ID: PMC8602730
Article link: Cell Syst
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: adnp ankrd11 arid1b atp1b2 atrx bptf braf cacna1a cdk13 chd4 chd7 chrd crebbp dnm1 dscam dyrk1a ehmt1 ep300 foxp1 grin2a grin2b igf1r kansl1 kat6a kcnq2 kdm5b kdm6a kmt2a kmt2c kmt2d kmt5b macrod2 mapt mecp2 med13l msl3 nalcn nf1 notch1 nsd1 pik3ca pogz prkce pten ptpn11 rabgap1l raf1 ret ryr3 scn2a setbp1 setd1a setd5 slc45a2 slc6a1 son sos1 srcap stx1b syn1 syngap1 thoc2 tiam1 trim9 trip12 usp34 wac zeb2
GO keywords: brain development [+]

Disease Ontology terms: autism spectrum disorder [+]

Article Images: [+] show captions
References [+] :
Abrahams, SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). 2013, Pubmed