Department of Pediatrics, Children's Hospital Medical Center, University Hospital Bonn, 53127 Bonn, Germany.
Institute of Human Genetics, University Hospital Bonn, 53127 Bonn, Germany.
Int J Mol Sci. 2020 Nov 3;21(21):8247. doi: 10.3390/ijms21218247.
The treatment of major birth defects are key concerns for child health. Hitherto, for the majority of birth defects, the underlying cause remains unknown, likely to be heterogeneous. The implicated mortality and/or reduced fecundity in major birth defects suggest a significant fraction of mutational de novo events among the affected individuals. With the advent of systematic array-based molecular karyotyping, larger cohorts of affected individuals have been screened over the past decade. This review discusses the identification of disease-causing copy-number variations (CNVs) among individuals with different congenital malformations. It highlights the differences in findings depending on the respective congenital malformation. It looks at the differences in findings of CNV analysis in non-isolated complex congenital malformations, associated with central nervous system malformations or intellectual disabilities, compared to isolated single organ-system malformations. We propose that the more complex an organ system is, and the more genes involved during embryonic development, the more likely it is that mutational de novo events, comprising CNVs, will confer to the expression of birth defects of this organ system.
重大出生缺陷的治疗是儿童健康的关键关注点。迄今为止，对于大多数出生缺陷，其根本原因仍然未知，可能具有异质性。重大出生缺陷所涉及的死亡率和/或生育力降低表明，受影响个体中存在相当一部分新生突变事件。随着系统的基于阵列的分子细胞遗传学的出现，过去十年中已经对更大的受影响个体队列进行了筛选。本综述讨论了在具有不同先天性畸形的个体中鉴定致病性拷贝数变异 (CNV)。它强调了根据各自的先天性畸形的发现的差异。它研究了非孤立性复杂先天性畸形中 CNV 分析的发现差异，这些畸形与中枢神经系统畸形或智力障碍相关，与孤立性单一器官系统畸形相比。我们提出，器官系统越复杂，胚胎发育过程中涉及的基因越多，新生突变事件（包括 CNV）就越有可能导致该器官系统的出生缺陷的表达。
