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Article: Mutations in Hnrnpa1 cause congenital heart defects
Title | Mutations in Hnrnpa1 cause congenital heart defects |
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Authors | |
Keywords | Cardiovascular disease Development Genetics Heart failure Organogenesis |
Issue Date | 2018 |
Publisher | American Society for Clinical Investigation. |
Citation | JCI insight, 2018, v. 3 n. 2, p. 98555 How to Cite? |
Abstract | Incomplete penetrance of congenital heart defects (CHDs) was observed in a mouse model. We hypothesized that the contribution of a major genetic locus modulates the manifestation of the CHDs. After genome-wide linkage mapping, fine mapping, and high-throughput targeted sequencing, a recessive frameshift mutation of the heterogeneous nuclear ribonucleoprotein A1 (Hnrnpa1) gene was confirmed (Hnrnpa1ct). Hnrnpa1 was expressed in both the first heart field (FHF) and second heart field (SHF) at the cardiac crescent stage but was only maintained in SHF progenitors after heart tube formation. Hnrnpa1ct/ct homozygous mutants displayed complete CHD penetrance, including truncated and incomplete looped heart tube at E9.5, ventricular septal defect (VSD) and persistent truncus arteriosus (PTA) at E13.5, and VSD and double outlet right ventricle at P0. Impaired development of the dorsal mesocardium and sinoatrial node progenitors was also observed. Loss of Hnrnpa1 expression leads to dysregulation of cardiac transcription networks and multiple signaling pathways, including BMP, FGF, and Notch in the SHF. Finally, two rare heterozygous mutations of HNRNPA1 were detected in human CHDs. These findings suggest a role of Hnrnpa1 in embryonic heart development in mice and humans. |
Persistent Identifier | http://hdl.handle.net/10722/251858 |
ISSN | 2023 Impact Factor: 6.3 2023 SCImago Journal Rankings: 2.970 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yu, Z | - |
dc.contributor.author | Tang, PL | - |
dc.contributor.author | Wang, J | - |
dc.contributor.author | Bao, S | - |
dc.contributor.author | Shieh, JT | - |
dc.contributor.author | Leung, AW | - |
dc.contributor.author | Zhang, Z | - |
dc.contributor.author | Gao, F | - |
dc.contributor.author | Wong, SY | - |
dc.contributor.author | Hui, AL | - |
dc.contributor.author | Gao, Y | - |
dc.contributor.author | Dung, N | - |
dc.contributor.author | Zhang, ZG | - |
dc.contributor.author | Fan, Y | - |
dc.contributor.author | Zhou, X | - |
dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Wong, DS | - |
dc.contributor.author | Sham, PC | - |
dc.contributor.author | Azhar, A | - |
dc.contributor.author | Kwok, PY | - |
dc.contributor.author | Tam, PP | - |
dc.contributor.author | Lian, Q | - |
dc.contributor.author | Cheah, KSE | - |
dc.contributor.author | Wang, B | - |
dc.contributor.author | Song, Y | - |
dc.date.accessioned | 2018-03-21T07:00:39Z | - |
dc.date.available | 2018-03-21T07:00:39Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | JCI insight, 2018, v. 3 n. 2, p. 98555 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.uri | http://hdl.handle.net/10722/251858 | - |
dc.description.abstract | Incomplete penetrance of congenital heart defects (CHDs) was observed in a mouse model. We hypothesized that the contribution of a major genetic locus modulates the manifestation of the CHDs. After genome-wide linkage mapping, fine mapping, and high-throughput targeted sequencing, a recessive frameshift mutation of the heterogeneous nuclear ribonucleoprotein A1 (Hnrnpa1) gene was confirmed (Hnrnpa1ct). Hnrnpa1 was expressed in both the first heart field (FHF) and second heart field (SHF) at the cardiac crescent stage but was only maintained in SHF progenitors after heart tube formation. Hnrnpa1ct/ct homozygous mutants displayed complete CHD penetrance, including truncated and incomplete looped heart tube at E9.5, ventricular septal defect (VSD) and persistent truncus arteriosus (PTA) at E13.5, and VSD and double outlet right ventricle at P0. Impaired development of the dorsal mesocardium and sinoatrial node progenitors was also observed. Loss of Hnrnpa1 expression leads to dysregulation of cardiac transcription networks and multiple signaling pathways, including BMP, FGF, and Notch in the SHF. Finally, two rare heterozygous mutations of HNRNPA1 were detected in human CHDs. These findings suggest a role of Hnrnpa1 in embryonic heart development in mice and humans. | - |
dc.language | eng | - |
dc.publisher | American Society for Clinical Investigation. | - |
dc.relation.ispartof | JCI insight | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Cardiovascular disease | - |
dc.subject | Development | - |
dc.subject | Genetics | - |
dc.subject | Heart failure | - |
dc.subject | Organogenesis | - |
dc.title | Mutations in Hnrnpa1 cause congenital heart defects | - |
dc.type | Article | - |
dc.identifier.email | Sham, PC: pcsham@hku.hk | - |
dc.identifier.email | Lian, Q: qzlian@hkucc.hku.hk | - |
dc.identifier.email | Cheah, KSE: hrmbdkc@hku.hk | - |
dc.identifier.email | Song, Y: songy@hku.hk | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.identifier.authority | Lian, Q=rp00267 | - |
dc.identifier.authority | Cheah, KSE=rp00342 | - |
dc.identifier.authority | Song, Y=rp00488 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1172/jci.insight.98555 | - |
dc.identifier.pmid | 29367466 | - |
dc.identifier.pmcid | PMC5821217 | - |
dc.identifier.scopus | eid_2-s2.0-85062247804 | - |
dc.identifier.hkuros | 289966 | - |
dc.identifier.volume | 3 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 98555 | - |
dc.identifier.epage | 98555 | - |
dc.identifier.isi | WOS:000423337400014 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2379-3708 | - |