Association of ventricular septal defect with rare variations of the HAND2 gene

LI Mei-Kun; PANG Shu-Chao; YAN Bo

doi:10.7499/j.issn.1008-8830.2212057

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Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (4) : 388-393. DOI: 10.7499/j.issn.1008-8830.2212057

CLINICAL RESEARCH

Association of ventricular septal defect with rare variations of the HAND2 gene

LI Mei-Kun, PANG Shu-Chao, YAN Bo

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Abstract

Objective To study the association of ventricular septal defect (VSD) with rare variations in the promoter region of HAND2 gene, as well as related molecular mechanisms. Methods Blood samples were collected from 349 children with VSD and 345 healthy controls. The target fragments were amplified by polymerase chain reaction and sequenced to identify the rare variation sites in the promoter region of the HAND2 gene. Dual-luciferase reporter assay was used to perform a functional analysis of the variation sites. Electrophoretic mobility shift assay (EMSA) was used to investigate related molecular mechanisms. TRANSFAC and JASPAR databases were used to predict transcription factors. Results Sequencing revealed that three variation sites (g.173530852A>G, g.173531173A>G, and g.173531213C>G) were only observed in the promoter region of the HAND2 gene in 10 children with VSD, among whom 4 children had only one variation site. The dual-luciferase reporter assay revealed that g.173531213C>G reduced the transcriptional activity of the HAND2 gene promoter. EMSA and transcription factor prediction revealed that g.173531213C>G created a binding site for transcription factor. Conclusions The rare variation, g.173531213C>G, in the promoter region of the HAND2 gene participates in the development and progression of VSD possibly by affecting the binding of transcription factors. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(4): 388-393

Key words

Ventricular septal defect / HAND2 gene / Rare variation / Child

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LI Mei-Kun, PANG Shu-Chao, YAN Bo. Association of ventricular septal defect with rare variations of the HAND2 gene[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(4): 388-393 https://doi.org/10.7499/j.issn.1008-8830.2212057

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