Analysis of HOXB1 gene in a cohort of patients with sporadic ventricular septal defect


Ventricular septal defect (VSD) including outlet VSD of double outlet right ventricle (DORV) and perimembranous VSD are among the most common congenital heart diseases found at birth. HOXB1 encodes a homeodomain transcription factor essential for normal cardiac outflow tract development. The aim of the present study was to investigate the possible genetic effect of sequence variations in HOXB1 on VSD. The coding regions and splice junctions of the HOXB1 gene were sequenced in 57 unrelated VSD patients. As a result, a homozygous c.74_82dup (p.Pro28delinsHisSerAlaPro) variant was identified in one individual with DORV. We also identified five previously reported polymorphisms (rs35114525, rs12946855, rs14534040, rs12939811, and rs7207109) in 18 patients (12 DORV and 6 perimembranous VSD). Our study did not show any pathogenic alterations in the coding region of HOXB1 among patients with VSD. To our knowledge this is the first study investigating the role of HOXB1 in nonsyndromic VSD, which provide more insight on the etiology of this disease.

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This work was supported by “AFM-Telethon” (MNH-Decrypt) and “ANR” (ANR-13-BSV2-0003) grants. A.P. received a PhD fellowship by the AFSMa (Association Française des Syndromes de Marfan et Apparentés). CARREG ( is supported by the Fondation cœur et artères and the Association pour la Recherche en Cardiologie du Fœtus à l’Adulte (ARCFA).

Author information




AP, NE, MG, JM, and JO performed the experiments. GC-B supervised the genetic and statistical analysis and drafted parts of the manuscript. FB and DB coordinated the CARREG protocol and validated the diagnosis of patients. SZ coordinate the genetic investigation and wrote the manuscript.

Corresponding author

Correspondence to Stéphane Zaffran.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study subjects included seventy-seven patients from the Necker-Enfants Malades Hospital. This study was approved by the Committee for the Protection of Persons (Comité de Protection des Personnes (CPP) Paris, France No. 2009-164).

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Informed consent was obtained from all patients for being included in the study.

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Pinard, A., Eudes, N., Mitchell, J. et al. Analysis of HOXB1 gene in a cohort of patients with sporadic ventricular septal defect. Mol Biol Rep 45, 1507–1513 (2018).

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  • Genetics
  • Ventricular septal defect
  • HOXB1
  • Variant
  • Congenital heart disease