English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

NSUN5 , encoding a cytosine-5 RNA methyltransferase and located in the 7q11.23 locus, is a candidate gene for tetralogy of Fallot (TOF). Deletion of the 7q11.23 locus in humans is linked to cardiac outflow tract (OFT) disorders including TOF. We identified four potential pathogenic mutations in the coding region of  NSUN5  and which were enriched in TOF patients by an association study of 132 TOF patients and 2,000 in-house controls ( P  = 1.44 × 10 –5 ). We then generated a  Nsun5  null ( Nsun5  –/– ) mouse model to validate the human findings by defining the functions of  Nsun5  in OFT morphogenesis. The OFT did not develop properly in the  Nsun5  deletion embryonic heart. We found a misalignment of the aorta and septum defects caused by the delayed fusion of the membraneous ventricular spetum as an OFT development delay. This caused OFT development delay in 27 of 64 (42.2%)  Nsun5  –/–  mice. Moreover, we also found OFT development delay in 8 of 51 (15.7%)  Nsun5  +/–  mice. Further functional experiments showed that the loss of  Nsun5  function impaired the 5-methylcytosine (m 5 C) modification and translation efficiency of essential cardiac genes.  Nsun5  is required for normal OFT morphogenesis and it regulates the m 5 C modification of essential cardiac genes. Our findings suggest the involvement of  NSUN5  in the pathogenesis of TOF.

Mutations in RNA Methyltransferase Gene NSUN5 Confer High Risk of Outflow Tract Malformation