Abnormal sodium channel mRNA splicing in hypertrophic cardiomyopathy

Adam M. Noyes, Anyu Zhou, Ge Gao, Lianzhi Gu, Sharlene Day, J. Andrew Wasserstrom, Samuel C. Dudley

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background Our previous studies showed that in ischemic and nonischemic heart failure (HF), the voltage-gated cardiac Na+ channel α subunit (SCN5A) mRNA is abnormally spliced to produce two truncated transcript variants (E28C and D) that activate the unfolded protein response (UPR). We tested whether SCN5A post-transcriptional regulation was abnormal in hypertrophic cardiomyopathy (HCM). Material and methods Human heart tissue was obtained from HCM patients. The changes in relative abundances of SCN5A, its variants, splicing factors RBM25 and LUC7A, and PERK, a major effector of the UPR, were analyzed by real time RT-PCR and the expression changes were confirmed by Western Blot. Results We found reduced full-length transcript, increased SCN5A truncation variants and activation of UPR in HCM when compared to control hearts. In these patients, real time RT-PCR revealed that HCM patients had decreased SCN5A mRNA to 27.8 ± 4.07% of control (P < 0.01) and an increased abundance of E28C and E28D (3.4 ± 0.3 and 2.8 ± 0.3-fold, respectively, P < 0.05). PERK mRNA increased 8.2 ± 3.1 fold (P < 0.01) in HCM patients. Western blot confirmed a significant increase of PERK. Conclusions These data suggested that the full-length SCN5A was reduced in patients with HCM. This reduction was accompanied by abnormal SCN5A pre-mRNA splicing and UPR activation. These changes may contribute to the arrhythmic risk in HCM.

Original languageEnglish (US)
Pages (from-to)282-286
Number of pages5
JournalInternational Journal of Cardiology
StatePublished - Dec 15 2017

Bibliographical note

Funding Information:
This work was supported by National Institute of Health (NIH R01HL106592 , R01HL104025 and R01HL119095 ).

Publisher Copyright:
© 2017 Elsevier B.V.


  • Human
  • Hypertrophic cardiomyopathy
  • Perk
  • SCN5A
  • Sodium channels
  • Splicing variants
  • Sudden cardiac death


Dive into the research topics of 'Abnormal sodium channel mRNA splicing in hypertrophic cardiomyopathy'. Together they form a unique fingerprint.

Cite this