Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease

被引:77
|
作者
Stallmeyer, B. [2 ]
Fenge, H.
Nowak-Goettl, U. [3 ]
Schulze-Bahr, E. [1 ,2 ]
机构
[1] Univ Hosp Muenster, Dept Cardiol & Angiol, D-48129 Munster, Germany
[2] Univ Munster, Interdisciplinary Ctr Clin Res IZKF, Munster, Germany
[3] Univ Childrens Hosp Muenster, Dept Pediat Hematol & Oncol, Munster, Germany
关键词
cardiac development; congenital heart disease; CSX; NKX2.5; ATRIAL SEPTAL-DEFECTS; HOMEODOMAIN; CSX/NKX2.5; GATA4; IDENTIFICATION; ANOMALIES; BLOCK; TBX5;
D O I
10.1111/j.1399-0004.2010.01422.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Heterozygous mutations in the human transcription factor gene NKX2.5 are associated with either isolated or combined congenital heart disease (CHD), primarily secundum atrial septal defect-II (ASD-II), ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Thus, NKX2.5 has an important role at different stages of cardiac development. The frequency of NKX2.5 mutations in a broader phenotypic spectrum of CHD is not completely determined. Here, we report the identification of two novel mutations in the NKX2.5 gene in a screening of 121 patients with a broad spectrum of CHDs. However, mutations were only associated with familial ASD-II and in both, patients also showed atrioventricular (AV) block. We found one missense mutation (R190L) in two siblings with ASD-II and a frame-shift mutation (A255fsX38) at the C-terminus in a mother and daughter. In addition, a single patient with hypoplastic left heart syndrome (HLHS) had the reported sequence variant R25C. Importantly, sporadic cases of CHD that share phenotypic aspects of NKX2.5 mutation carriers were negative for genetic analysis. Thus, even important for cardiac development, germline mutations in NKX2.5 are rare in patients with sporadic CHD and genetic and/or pathophysiologic heterogeneity is likely for sporadic forms of CHD.
引用
收藏
页码:533 / 540
页数:8
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