TY - JOUR
T1 - A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect
AU - Fardoun, Manal
AU - Dehaini, Hassan
AU - Kamar, Amina
AU - Bitar, Fadi
AU - Majdalani, Marianne
AU - El-Rassi, Issam
AU - Nemer, Georges
AU - Arabi, Mariam
N1 - Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/6/15
Y1 - 2019/6/15
N2 - Congenital heart defects (CHDs) are the leading cause of death in infants under 1 year of age. Aberrations in the expression and function of cardiac transcription factors (TFs) are a major contributor to CHDs. Despite the numerous studies undertaken to functionally characterize these TFs, their exact role in different stages of cardiogenesis is still not fully elucidated. Here we focused on HEY2, a basic helix loop helix transcriptional repressor, and its potential role in human ventricular septal defects. Genetic analysis was performed based on sequencing of DNA and cDNA obtained from post-operational cardiac tissues and blood of 17 Lebanese patients with various CHDs. The screen covered the entire coding regions of the GATA4, NKX2.5, TBX5, TBX20 and HEY2 genes. Our results revealed two novel somatic mutations, namely p.Ala229Thr and p.161_190 del, affecting HEY2 in the diseased cardiac tissues of two patients with VSD. These results suggest a potential role of HEY2 in regulating ventricular septation in humans.
AB - Congenital heart defects (CHDs) are the leading cause of death in infants under 1 year of age. Aberrations in the expression and function of cardiac transcription factors (TFs) are a major contributor to CHDs. Despite the numerous studies undertaken to functionally characterize these TFs, their exact role in different stages of cardiogenesis is still not fully elucidated. Here we focused on HEY2, a basic helix loop helix transcriptional repressor, and its potential role in human ventricular septal defects. Genetic analysis was performed based on sequencing of DNA and cDNA obtained from post-operational cardiac tissues and blood of 17 Lebanese patients with various CHDs. The screen covered the entire coding regions of the GATA4, NKX2.5, TBX5, TBX20 and HEY2 genes. Our results revealed two novel somatic mutations, namely p.Ala229Thr and p.161_190 del, affecting HEY2 in the diseased cardiac tissues of two patients with VSD. These results suggest a potential role of HEY2 in regulating ventricular septation in humans.
KW - Cardiac transcription factors
KW - Congenital heart defects
KW - HEY2
KW - Mutation
KW - Ventricular septal defect
UR - http://www.scopus.com/inward/record.url?scp=85064330498&partnerID=8YFLogxK
U2 - 10.1007/s00246-019-02099-y
DO - 10.1007/s00246-019-02099-y
M3 - Article
C2 - 30955100
AN - SCOPUS:85064330498
SN - 0172-0643
VL - 40
SP - 1084
EP - 1091
JO - Pediatric Cardiology
JF - Pediatric Cardiology
IS - 5
ER -