Genetic disorders of cardiac morphogenesis. The DiGeorge and velocardiofacial syndromes.
Genetic disorders of cardiac morphogenesis. The DiGeorge and velocardiofacial syndromes.
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心脏形态发生的遗传性疾病。
DOI：
10.1161/01.res.80.4.437
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发表时间：
1997
影响因子：
20.1
通讯作者：
Emanuel,BS
中科院分区：
文献类型：
--
作者：
Goldmuntz,E;Emanuel,BS
先天性心脏缺陷被认为是由各种遗传和环境影响造成的。虽然大多数CHD是作为偶发事件发生的，但许多缺陷是明确定义的遗传综合征的一部分。与一般人群相比，在综合征的背景下，特定类型的CHD通常比例过高。该综合征的遗传病因的鉴定可能有助于了解相关心脏畸形的病因。因此，由于圆锥动脉干心脏缺陷是DGS的主要特征，这种综合征的特定遗传病因已成为心脏病学家和心脏发育生物学家的极大兴趣。尽管表型高度可变，但DGS的典型特征是胸腺发育不全或发育不全、甲状旁腺发育不全或发育不全、圆锥干心脏缺陷和轻度畸形的面部特征。最常见的心脏缺陷包括动脉干、主动脉弓中断和法洛四联症。3.多器官系统的缺陷，在胚胎发生过程中由共同的前体同时产生，导致DGS是一种发育领域缺陷的建议。[4]发育场是指表现为一个协调的发育单位的胚胎细胞群。这种”形态发生反应单位”的破坏导致特定的表型，其可能涉及许多不同的终末器官，并且可能根据扰动的时间和性质而在表型上可变。不同的因素，如遗传改变或环境损伤，可能会破坏正常的形态发生的反应单位，并导致类似的phenotype.Preliminary证据表明，在DGS的情况下，形态发生反应单位是头和颅神经嵴。在鸡和啮齿动物中的实验已经证明，来自耳前和耳后尾侧后脑的神经嵴细胞形成第三和第四弓/囊的间充质。第三和第四鳃弓/囊产生胸腺、甲状旁腺、主动脉和头颈血管。此外，神经嵴细胞从
Congenital heart defects are thought to result from a variety of genetic and environmental influences. Although most CHD occurs as a sporadic event, many defects are part of a well-defined genetic syndrome. Particular types of CHD are often overrepresented in the context of a syndrome compared with the general population. Identification of the genetic etiology of the syndrome may lend insight into the etiology of the associated cardiac malformation. Thus, because conotruncal cardiac defects are a cardinal feature of DGS, the specific genetic etiology of this syndrome has become of great interest to the cardiologist and cardiac developmental biologist. Although the phenotype is highly variable, DGS is typically characterized by aplasia or hypoplasia of the thymus, aplasia or hypoplasia of the parathyroid glands, conotruncal cardiac defects, and mildly dysmorphic facial features. 12 The most common cardiac defects include truncus arteriosus, interrupted aortic arch, and tetralogy of Fallot. 3 Defects in multiple organ systems, which arise concurrently and from common precursors during embryogenesis, have led to the proposal that DGS is a developmental field defect. 4 A developmental field refers to a population of embryonic cells that behave as a single coordinated developmental unit. Disruption of this" morphogenetically reactive unit" results in a particular phenotype, which may involve many different end organs and may be phenotypically variable depending upon the timing and nature of the perturbation. Different factors, such as genetic alterations or environmental insults, could disrupt the normal morphogenesis of the reactive unit and result in a similar phenotype.Preliminary evidence suggests that in the case of DGS, the morphogenetically reactive unit is the cephalic and cranial neural crest. Experiments in the chicken and rodent have demonstrated that neural crest cells from the preotic and postotic caudal hindbrain form the mesenchyme of the third and fourth arches/pouches. The third and fourth branchial arches/pouches give rise to the thymus, parathyroid glands, aorta, and head and neck vessels. Moreover, neural crest cells from the