The Section of Pediatric Cardiology, Texas Children's Hospital, Houston, Texas 77030, USA.
Am J Med Genet A. 2011 Sep;155A(9):2215-20. doi: 10.1002/ajmg.a.34129. Epub 2011 Aug 10.
Interstitial deletion of chromosome 8p23.1 has been reported in patients with congenital heart defects, including atrial and ventricular septal defects, pulmonary stenosis, and complex cyanotic heart defects. GATA4, a zinc-finger transcription factor gene, has been localized to this region. GATA4 interacts with additional transcription factors in the embryogenesis of the primitive heart tube. Mutations in GATA4 are thought to be responsible for the congenital heart defects reported in association with this chromosomal deletion, and several familial point mutations leading to amino acid substitutions have also been identified. Left ventricular noncompaction (LVNC) is a clinically heterogeneous disorder characterized by LV myocardial trabeculations and intertrabecular recesses that communicate with the LV cavity. Patients may be asymptomatic or may present with evidence of severely depressed LV systolic and diastolic function. The LV may be dilated or hypertrophied, and clinical expression may be undulating. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A 12-year-old boy with a history of acute lymphoblastic leukemia, dysmorphic features, and LVNC with preserved LV systolic function was referred to the Cardiovascular Genetics Clinic at our institution. The patient was asymptomatic in terms of cardiovascular function. Chromosome microarray testing revealed an interstitial deletion in the region of 8p23.1 containing GATA4. LVNC has not been reported previously in association with this chromosome deletion. Further investigation into the role of GATA4 in patients with LVNC is warranted.
8p23.1 染色体片段缺失已在伴有先天性心脏缺陷(包括房间隔和室间隔缺损、肺动脉瓣狭窄和复杂紫绀型心脏缺陷)的患者中报道。锌指转录因子基因 GATA4 已定位至该区域。GATA4 在原始心脏管的胚胎发生过程中与其他转录因子相互作用。据认为,GATA4 突变是与该染色体缺失相关的报道的先天性心脏缺陷的原因,并且已经鉴定出几个导致氨基酸取代的家族点突变。左心室心肌致密化不全(LVNC)是一种临床表现高度异质性的疾病,其特征为左心室心肌小梁和小梁间陷窝与左心室腔相通。患者可能无症状,也可能表现为左心室收缩和舒张功能严重受损的证据。左心室可能扩张或肥厚,临床表现可能波动。已报道了几种 LVNC 的遗传病因,具有不同的遗传方式,包括常染色体显性遗传和 X 连锁遗传,但已鉴定出的相关基因相对较少。一名 12 岁男孩,有急性淋巴细胞白血病病史、畸形特征和伴有左心室收缩功能保留的 LVNC,被转介至我们机构的心血管遗传学诊所。该患者心血管功能无症状。染色体微阵列检测显示 8p23.1 区域存在包含 GATA4 的染色体片段缺失。此前尚未报道过该染色体缺失与 LVNC 相关。需要进一步研究 GATA4 在 LVNC 患者中的作用。