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Abstract：
OBJECTIVE: Atrial septal defect (ASD) is the second most common congenital heart defect (CHD) and is observed in families as an autosomal dominant trait as well as in nonfamilial CHD. Mutations in the NKX2-5 gene, located on chromosome 5, are associated with ASD, often combined with conduction disturbances, cardiomyopathies, complex CHD, and sudden cardiac death as well. Here, we show that NKX2-5 mutations primarily occur in ASD patients with conduction disturbances and heritable ASD. Furthermore, these families are at increased risk of sudden cardiac death.
RESULTS: We screened 39 probands with familial CHD for mutations in NKX2-5 and discovered a novel mutation in one family (2.5%) with ASD and atrioventricular block. A review of the literature revealed 59 different NKX2-5 mutations in 202 patients. Mutations were significantly more common in familial cases compared to nonfamilial cases (P = 7.1 × 10(-9) ). The majority of patients (74%) had ASD with conduction disturbance. Nineteen patients (15%) of 120 with familial ASD and conduction disturbance died from sudden cardiac death of which nine (8%) were confirmed mutation carriers, and 10 were possible carriers.
CONCLUSIONS: NKX2-5 mutations mainly occur in familial CHD, the signature phenotype is ASD with conduction disturbances and mutation carriers are at increased risk of sudden cardiac death. We suggest that familial ASD patients should be screened for NKX2-5 mutations and, if they are mutation carriers, implantation of an implantable cardioverter-defibrillator should be considered in these patients.
RESULTS: We screened 39 probands with familial CHD for mutations in NKX2-5 and discovered a novel mutation in one family (2.5%) with ASD and atrioventricular block. A review of the literature revealed 59 different NKX2-5 mutations in 202 patients. Mutations were significantly more common in familial cases compared to nonfamilial cases (P = 7.1 × 10(-9) ). The majority of patients (74%) had ASD with conduction disturbance. Nineteen patients (15%) of 120 with familial ASD and conduction disturbance died from sudden cardiac death of which nine (8%) were confirmed mutation carriers, and 10 were possible carriers.
CONCLUSIONS: NKX2-5 mutations mainly occur in familial CHD, the signature phenotype is ASD with conduction disturbances and mutation carriers are at increased risk of sudden cardiac death. We suggest that familial ASD patients should be screened for NKX2-5 mutations and, if they are mutation carriers, implantation of an implantable cardioverter-defibrillator should be considered in these patients.
摘要：
目的：房间隔缺损（ASD）是第二常见的先天性心脏病（CHD），在家庭和非家族性CHD中都具有常染色体显性性状。NKX2-5基因突变,位于5号染色体上，与ASD相关，通常与传导紊乱相结合，心肌病,复杂的CHD,还有心源性猝死.这里,我们显示NKX2-5突变主要发生在有传导障碍和遗传性ASD的ASD患者中.此外，这些家庭心源性猝死的风险增加。
结果：我们筛选了39位患有家族性CHD的先证者的NKX2-5突变，并在一个患有ASD和房室传导阻滞的家族（2.5％）中发现了一个新的突变。文献综述揭示了202例患者中59种不同的NKX2-5突变。与非家族性病例相比，家族性病例中的突变明显更常见（P=7.1×10（-9））。大多数患者（74％）患有传导障碍的ASD。120例家族性ASD和传导障碍患者中有19例（15％）死于心源性猝死，其中9例（8％）是确诊的突变携带者。和10个可能的载体。
结论：NKX2-5突变主要发生在家族性CHD,特征表型为ASD伴传导紊乱,突变携带者心源性猝死风险增加.我们建议家族性ASD患者应筛查NKX2-5突变，如果他们是突变携带者，这些患者应考虑植入植入式心律转复除颤器.
结果：我们筛选了39位患有家族性CHD的先证者的NKX2-5突变，并在一个患有ASD和房室传导阻滞的家族（2.5％）中发现了一个新的突变。文献综述揭示了202例患者中59种不同的NKX2-5突变。与非家族性病例相比，家族性病例中的突变明显更常见（P=7.1×10（-9））。大多数患者（74％）患有传导障碍的ASD。120例家族性ASD和传导障碍患者中有19例（15％）死于心源性猝死，其中9例（8％）是确诊的突变携带者。和10个可能的载体。
结论：NKX2-5突变主要发生在家族性CHD,特征表型为ASD伴传导紊乱,突变携带者心源性猝死风险增加.我们建议家族性ASD患者应筛查NKX2-5突变，如果他们是突变携带者，这些患者应考虑植入植入式心律转复除颤器.
