A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect

Fardoun, Manal; Dehaini, Hassan; Kamar, Amina; Bitar, Fadi; Majdalani, Marianne; El‐Rassi, Issam; Nemer, Georges; Arabi, Mariam

doi:10.1007/s00246-019-02099-y

Cited by 5 publications

(3 citation statements)

References 23 publications

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“… 23 , 24 Two studies did report on finding HEY2 variants in cardiac tissue of CHD patients, but it is unclear if these variants were causative. 25 , 26 , 27 Furthermore, a variant near HEY2 was identified as a risk factor for Brugada Syndrome, a cardiac arrhythmia disorder, through a genome-wide association study. 28 …”

Section: Discussionmentioning

confidence: 99%

Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms

Walree

Dombrowsky

Jansen

et al. 2021

Genetics in Medicine

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Section: Discussionmentioning

confidence: 99%

Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms

Walree

Dombrowsky

Jansen

et al. 2021

Genetics in Medicine

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“…SCN5A is closely related to arrhythmia (Han et al, 2018). Of note, HEY2 is a member of the bHLH transcription inhibitor family, the non-synonymous mutations of HEY2 are related to cardiac malfor-mations, such as congenital ventricular septal defect (Fardoun et al, 2019). Therefore, GATA5 participates in the regulation of various congenital heart diseases through a GATA5/cx36.7/NKX2-5/HEY2 signaling pathway (Fig.…”

Section: Gata5/connexin 367(cx367)/nkx2-5/hey2 Signaling Pathwaymentioning

confidence: 99%

Potential roles of GATA binding protein 5 in cardiovascular diseases

Song

Yan

2020

Reviews in Cardiovascular Medicine

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“…Some studies illustrated somatic variants in the cardiogenic transcription factors NKX2-5 and TBX5 in formalin-fixed CHD hearts [ 7 , 8 , 9 ]; however, these findings could not be consistently confirmed in subsequent studies using freshly frozen cardiac tissue. The debate on the role of somatic variants, either as a causal or contributing factor to CHD, has still not been settled [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA

Meerschaut

Steyaert

Bové

et al. 2022

Genes

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Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In contrast to syndromic CHD (SCHD), the genetic basis of isolated CHD (ICHD) is complex, and the underlying pathogenic mechanisms appear intricate and are incompletely understood. Next to rare Mendelian conditions, somatic mosaicism or a complex multifactorial genetic architecture are assumed for most ICHD. We performed exome sequencing (ES) in 73 parent–offspring ICHD trios using proband DNA extracted from cardiac tissue. We identified six germline de novo variants and 625 germline rare inherited variants with ‘damaging’ in silico predictions in cardiac-relevant genes expressed in the developing human heart. There were no CHD-relevant somatic variants. Transmission disequilibrium testing (TDT) and association testing (AT) yielded no statistically significant results, except for the AT of missense variants in cilia genes. Somatic mutations are not a common cause of ICHD. Rare de novo and inherited protein-damaging variants may contribute to ICHD, possibly as part of an oligogenic or polygenic disease model. TDT and AT failed to provide informative results, likely due to the lack of power, but provided a framework for future studies in larger cohorts. Overall, the diagnostic value of ES on cardiac tissue is limited in individual ICHD cases.

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A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect

Cited by 5 publications

References 23 publications

Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms

Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms

Potential roles of GATA binding protein 5 in cardiovascular diseases

Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA

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