Nouira Sonia, Kamoun Ikram, Ouragini Houyem, Charfeddine Cherine, Mahjoub Haifa, Ouechtati Farah, Bchetnia Mbarka, Ben Halima Afef, Abdelhak Sonia, Kachboura Salem
Molecular Investigation of Genetic "Disorders by Diseases" Research Unit 26/04, Institut Pasteur de Tunis, Tunisia.
Arch Med Res. 2008 May;39(4):429-33. doi: 10.1016/j.arcmed.2008.01.002. Epub 2008 Feb 13.
Atrial septal defect (ASD) is an autosomal dominant disease characterized by left-to-right shunting and increased right ventricular output. Approximately 5-10% of congenital heart diseases (CHD) are due to ASD, which is one of the most frequent CHD found in adults. The gene responsible for ASD was mapped to chromosome 5q35 encoding the transcription factor NKX2-5 that plays an important role for the regulation of septation during cardiac morphogenesis.
A Tunisian family including four affected members was investigated. Individuals were genotyped using the polymorphic microsatellite markers D5S394 and D5S2069 overlapping the NKX2-5 gene.
We report here clinical and molecular investigation of a Tunisian consanguineous family with four affected members. Two presented with ASD associated with prolonged PR interval, whereas the other two presented only a prolonged PR interval. We also identified five asymptomatic individuals in the same family with ventricular preexcitation. Although the patients were products of a consanguineous marriage, no other abnormalities were observed in this family. Genotyping and linkage analysis showed exclusion of linkage between the gene responsible for ASD in this family and NKX2.5 gene.
Our results further confirm the genetic heterogeneity of ASD.
房间隔缺损（ASD）是一种常染色体显性疾病，其特征为左向右分流和右心室输出增加。先天性心脏病（CHD）中约5%-10%由ASD引起，ASD是成人中最常见的CHD之一。导致ASD的基因定位于5q35染色体，该染色体编码转录因子NKX2-5，其在心脏形态发生过程中对隔膜形成的调节起重要作用。
对一个包括四名患病成员的突尼斯家庭进行了调查。使用与NKX2-5基因重叠的多态微卫星标记D5S394和D5S2069对个体进行基因分型。
我们在此报告对一个有四名患病成员的突尼斯近亲家庭进行的临床和分子研究。两名患者表现为ASD并伴有PR间期延长，而另外两名仅表现为PR间期延长。我们还在同一家庭中发现了五名无症状的心室预激个体。尽管这些患者是近亲结婚的产物，但该家庭未观察到其他异常。基因分型和连锁分析表明，该家庭中导致ASD的基因与NKX2.5基因之间不存在连锁关系。
我们的结果进一步证实了ASD的遗传异质性。
