Atrioventricular canal defect in patients with RASopathies
Atrioventricular canal defect in patients with RASopathies
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DOI：
10.1038/ejhg.2012.145
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发表时间：
2013-02-01
影响因子：
5.2
通讯作者：
Dallapiccola, Bruno
中科院分区：
文献类型：
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作者：
Digilio, Maria Cristina;Lepri, Francesca Romana;Dallapiccola, Bruno
先天性心脏缺陷影响60-85%的RASopathies患者。我们分析了在RAS/MAPK通路中起作用的蛋白质编码基因突变患者的房室通道缺陷的临床和分子特征。在2002年至2011年期间，收集了101名患有心脏缺陷和分子证实的RAS病的患者。在8/101（8%）例患者中诊断出完全或部分（包括二尖瓣裂）房室管缺陷范围内的先天性心脏缺陷，包括7例PTPN 11基因突变和1例RAF 1基因突变。唯一的复发突变是PTPN 11中的错义PTPN 11 c.124A>G变化（T42 A）。部分性房室管缺损6例，完全性房室管缺损1例，二尖瓣裂1例。在4例受试者中，该缺陷与其他心脏缺陷相关，包括主动脉瓣下狭窄、二尖瓣畸形、肺动脉瓣狭窄和肥厚性心肌病。PTPN 11和RAF 1基因突变的母亲分离分别发生在两名和一名患者。PTPN 11基因突变的家系中患侧先天性心脏病的发生率不一致，RAF 1基因突变的家系中患侧先天性心脏病的发生率一致。总之，我们的数据证实了以前的报告表明，房室管缺损是努南综合征的一个相对常见的特点。在RASopathy中，观察到房室管缺陷在PTPN 11突变受试者中的发生率较高，尽管这种关联可能由于统计功效低而不显著。在RASopathies家族的遗传咨询中，应考虑房室管缺陷的家族分离。European Journal of Human Genetics（2013）21，200-204; doi：10.1038/ejhg.2012.145; 2012年7月11日在线发表
Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies. European Journal of Human Genetics (2013) 21, 200-204; doi:10.1038/ejhg.2012.145; published online 11 July 2012