A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family -: art. no. e97
A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family -: art. no. e97
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DOI：
10.1136/jmg.2004.018895
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发表时间：
2004-07-01
影响因子：
4
通讯作者：
Matsumoto, N
中科院分区：
文献类型：
--
作者：
Okubo, A;Miyoshi, O;Matsumoto, N
一个由四代共29名成员组成的日本大家庭，其中11名成员患有ASD（I-1、II-2、II-6、II-7、III-1、III-2、III-4、IV-1、IV-2、IV-5和IV-6;图1A）。5名患者（II-7、III-1、III-2、IV-1和IV-2）的ASD接受了手术修复，2名患者（II-2和IV-1）还患有肺动脉狭窄（PS）。8例受试者的心脏缺陷（II-2、II-7、III-1、III-2、IV-1和IV-2），包括2例患病受试者（I-1和II-6）是由共同作者之一（BK）根据病史、手术记录、12导联心电图和彩色多普勒超声心动图（图1A）进行临床诊断的，而另外3例受试者（III-4、IV-5和IV-6）使用由下文描述的突变分析提供的信息回顾性地发现。11名受影响的成员中没有任何其他心脏传导系统或其他器官的异常。在获得知情同意后，从22名家系成员外周血白细胞中提取DNA，进行连锁和突变分析，在8 p23的GATA 4周围的11个微卫星标记位点对22名家系成员进行连锁分析（D8 S561、D8 S503、D8 S1721、D8 S550、D8 S265、D8 S552、D8 S1790、D8 S549、D8 S254、D8 S258和D8 S1771），并使用计算机程序MLINK（FASTLINK软件，版本4.1P）进行两点连锁分析，如前所述。11 III-4、IV-5和IV-6在该初始连锁分析中被视为未受影响。
METHODS Subjects A large Japanese family composed of a total of 29 members across four generations contained 11 members with ASD (I-1, II-2, II-6, II-7, III-1, III-2, III-4, IV-1, IV-2, IV-5, and IV-6; fig 1A). ASD in five patients (II-7, III-1, III-2, IV-1, and IV-2) was surgically repaired, and two patients (II-2 and IV-1) also had pulmonary stenosis (PS). The heart defects in eight subjects (II-2, II-7, III-1, III-2, IV-1, and IV-2) including two diseased subjects (I-1 and II-6) had been clinically diagnosed by one of co-authors (BK) on the basis of their past histories, operation records, 12-lead electrocardiograms, and echocardiograms with colour Doppler apparatus (fig 1A), while those in three other subjects (III-4, IV-5, and IV-6) were retrospectively found using information provided by the mutation analysis described below. None of the 11 affected members had any other abnormalities in the cardiac conduction system or other organs. After informed consent was obtained, DNA was extracted from peripheral blood leukocytes of 22 family members.Linkage and mutation analyses Linkage analysis was performed in 22 family members at 11 microsatellite marker loci around GATA4 at 8p23 (D8S561, D8S503, D8S1721, D8S550, D8S265, D8S552, D8S1790, D8S549, D8S254, D8S258, and D8S1771), and two-point linkage analysis was carried out using the computer program MLINK (FASTLINK software, version 4.1 P), as described previously. 11 III-4, IV-5, and IV-6 were regarded as unaffected at this initial linkage analysis.