de Ravel T J L, Balikova I, Thienpont B, Hannes F, Maas N, Fryns J-P, Devriendt K, Vermeesch J R
Centre for Human Genetics, UZ Gasthuisberg, Leuven, Belgium.
Cytogenet Genome Res. 2006;115(3-4):225-30. doi: 10.1159/000095918.
Molecular karyotyping has revealed that microdeletions/duplications in the human genome are a major cause of multiple congenital anomalies associated with mental retardation (MCA/MR). The identification of a de novo chromosomal imbalance in a patient with MCA/MR is usually considered causal for the phenotype while a chromosomal imbalance inherited from a phenotypically normal parent is considered as a benign variation and not related to the disorder. Around 40% of imbalances in patients with MCA/MR in this series is inherited from a healthy parent and the majority of these appear to be (extremely) rare variants. As some of these contain known disease-causing genes and have also been found to be de novo in MCA/MR patients, this challenges the general view that such familial variants are innocent and of no major phenotypic consequence. Rather, we argue, that human genomes can be tolerant of genomic copy number variations depending on the genetic and environmental background and that different mechanisms play a role in determining whether these chromosomal imbalances manifest themselves.
分子核型分析显示，人类基因组中的微缺失/微重复是导致多种先天性异常伴智力障碍（MCA/MR）的主要原因。在患有MCA/MR的患者中，鉴定出的新发染色体失衡通常被认为是导致该表型的原因，而从表型正常的父母遗传而来的染色体失衡则被视为良性变异，与该疾病无关。在本系列MCA/MR患者中，约40%的失衡是从健康父母遗传而来的，其中大多数似乎是（极其）罕见的变异。由于其中一些包含已知的致病基因，并且在MCA/MR患者中也被发现是新发的，这挑战了普遍观点，即此类家族性变异是无害的，不会产生重大表型后果。相反，我们认为，人类基因组可以根据遗传和环境背景容忍基因组拷贝数变异，并且不同的机制在决定这些染色体失衡是否表现出来方面发挥作用。
