Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province 215002, PR China.
Clin Chim Acta. 2010 Nov 11;411(21-22):1741-5. doi: 10.1016/j.cca.2010.07.021. Epub 2010 Jul 24.
Previous studies have identified that mutations in a few genes, including T-BOX5, NKX2-5, EVC and GATA4, are associated with atrial septal defect (ASD).
A family of three generations with 4 members who were affected with ASD was investigated. To exclude the presence of any sub-microscopic chromosomal imbalance, high-resolution 1M array-based comparative genomic hybridization (aCGH) was performed. SNaPShot was used to certify the specificity of the finding mutation in the other family members. The coding region of GATA4 and NKX2-5 genes was screened by sequencing in another 30 cases including 10 cases of ventricular septal defect (VSD), 10 cases of atrial septal defect (ASD), 8 cases of VSD combined with ASD and 2 cases of atrioventricular septal defects (AVSD).
No pathogenic copy number variant was detected by aCGH in the four affected family members with ASD. A novel non-synonymous variant, c.839C>T (T280M) in GATA4, was identified and segregated with all the ASD patients within this Chinese family. Such mutation was absent in other family members or present among sporadic CHD patients. In addition, we identified a non-synonymous variant in the NKX2-5 gene (P257A) associated with one congenital heart disease patient with VSD. Both mutations were not identified among healthy controls.
T280M mutation of GATA4 is suggested to be associated with ASD in this Chinese family.
先前的研究已经确定了一些基因（包括 T-BOX5、NKX2-5、EVC 和 GATA4）的突变与房间隔缺损（ASD）有关。
对一个三代同堂的 4 名 ASD 患者家系进行了研究。为排除任何亚微染色体不平衡的存在，进行了高分辨率 1M 阵列比较基因组杂交（aCGH）。SNaPShot 用于验证其他家族成员中发现突变的特异性。通过对另外 30 例病例（包括 10 例室间隔缺损（VSD）、10 例房间隔缺损（ASD）、8 例 VSD 合并 ASD 和 2 例房室间隔缺损（AVSD））的 GATA4 和 NKX2-5 基因的编码区进行测序，筛选出这些病例。
在 4 名患有 ASD 的受影响家族成员中，aCGH 未检测到致病性拷贝数变异。在这个中国家系中，发现了一个新的非同义突变 c.839C>T（T280M），该突变与所有 ASD 患者共分离。这种突变不存在于其他家族成员中，也不存在于散发性 CHD 患者中。此外，我们在一个患有 VSD 的先天性心脏病患者中发现了 NKX2-5 基因的一个非同义突变（P257A）。这两种突变在健康对照组中均未被识别。
在这个中国家系中，GATA4 的 T280M 突变被认为与 ASD 有关。
