Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics Department of Cardiothoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Clin Genet. 2012 Nov;82(5):466-71. doi: 10.1111/j.1399-0004.2011.01787.x. Epub 2011 Oct 30.
Congenital heart defects (CHDs) occur in about 0.5-1% of all newborns and are the most common birth defects. Double outlet right ventricle (DORV) accounts for approximately 1-3% of all CHDs. Similar to Tetralogy of Fallot (TOF), DORV is a subtype of contruncal heart defects (CTDs) and is anatomically characterized by a malposition of the great arteries. We described a boy with chromosomal translocation: 46, XY t (8; 18) (q22; q21) that may disrupts the ZFPM2/FOG2 locus. The coding sequences of ZFPM2/FOG2 were determined in 38 patients with sporadic DORV, 95 patients with TOF, and 12 patients with transposition of the great arteries. Five DNA sequence variants affecting variably conserved residues of ZFPM2/FOG2 were identified in patients with TOF type or ventricular septal defect type of DORV. Three novel mutations (p.V339I, p.K737E, and p.A611T) were reported for the first time. The other two mutations (p.M703L and p.Q889E) were reported in patients with congenital diaphragmatic hernia but not in patients with CHD. Our finding suggests that variants of the ZFPM2/FOG2 gene might be a common cause of DORV.
先天性心脏缺陷 (CHD) 约占所有新生儿的 0.5-1%，是最常见的出生缺陷。双出口右心室 (DORV) 约占所有 CHD 的 1-3%。与法洛四联症 (TOF) 相似，DORV 是一种共同动脉干心脏缺陷 (CTD) 的亚型，解剖学上表现为大动脉位置异常。我们描述了一名患有染色体易位的男孩：46,XY t (8; 18) (q22; q21)，可能破坏了 ZFPM2/FOG2 基因座。在 38 名散发性 DORV 患者、95 名 TOF 患者和 12 名大动脉转位患者中确定了 ZFPM2/FOG2 的编码序列。在 TOF 型或 DORV 的室间隔缺损型患者中发现了影响 ZFPM2/FOG2 可变保守残基的 5 种 DNA 序列变异。首次报道了 3 种新突变 (p.V339I、p.K737E 和 p.A611T)。另外两种突变 (p.M703L 和 p.Q889E) 已在患有先天性膈疝的患者中报道过，但未在患有 CHD 的患者中报道过。我们的发现表明，ZFPM2/FOG2 基因突变可能是 DORV 的常见原因。
