Pinard Amélie, Eudes Nathalie, Mitchell Julia, Bajolle Fanny, Grelet Maude, Okoronkwo Joséphine, Bonnet Damien, Collod-Béroud Gwenaelle, Zaffran Stéphane
Aix Marseille Université, INSERM U1251, MMG, Marseille, France.
Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Mol Biol Rep. 2018 Oct;45(5):1507-1513. doi: 10.1007/s11033-018-4212-x. Epub 2018 Jun 19.
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.
室间隔缺损(VSD),包括双出口右心室(DORV)的流出道室间隔缺损和膜周部室间隔缺损,是出生时发现的最常见的先天性心脏病之一。HOXB1编码一种对正常心脏流出道发育至关重要的同源结构域转录因子。本研究的目的是调查HOXB1序列变异对室间隔缺损可能的遗传影响。对57名无亲缘关系的室间隔缺损患者的HOXB1基因编码区和剪接位点进行了测序。结果,在一名双出口右心室患者中鉴定出一个纯合的c.74_82dup(p.Pro28delinsHisSerAlaPro)变异。我们还在18名患者(12名双出口右心室患者和6名膜周部室间隔缺损患者)中鉴定出5个先前报道的多态性(rs35114525、rs12946855、rs14534040、rs12939811和rs7207109)。我们的研究未显示室间隔缺损患者中HOXB1编码区有任何致病性改变。据我们所知,这是第一项研究HOXB1在非综合征性室间隔缺损中作用的研究,为该病的病因提供了更多见解。