Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports
Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports
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DOI：
10.1136/jmg.2005.039453
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发表时间：
2006-08-01
影响因子：
4
通讯作者：
Vermeesch, J. R.
中科院分区：
文献类型：
--
作者：
Menten, B.;Maas, N.;Vermeesch, J. R.
背景：染色体异常是智力低下和多先天畸形（MCA/MR）的主要原因。这些染色体不平衡的筛查主要通过标准核型分析来完成。先前对染色体表型和正常核型的患者进行的阵列CGH研究表明，10-15%的先前未被注意到的新发染色体不平衡的发生率。（迄今为止发表的最大的）特发性MCA/MR但核型正常。在140例患者中的28例（20%）中检测到亚显微镜下染色体不平衡，包括18例缺失，7例重复和3例不平衡易位。24例失衡中有17例被重新确认，19例被假定为因果关系。排除亚端粒失衡，我们的研究确定了11个临床相关的间质亚显微失衡（8%）。考虑到这一点和以前报道的研究，阵列CGH筛查分辨率至少为1 Mb已进行了432例MCA/MR患者。大多数不平衡是非复发性的，分布在整个基因组。在至少8.8%的这些患者（38 432）从头intrachromosomal alterations已被identified.Conclusions：阵列CGH应被认为是一个重要方面的MCA/MR患者的遗传分析。此外，在本研究中，三名患者镶嵌结构染色体重排。这些患者中的一个在少至8%的细胞中具有单体7，表明阵列CGH允许检测低等级嵌合体。
Background: Chromosomal abnormalities are a major cause of mental retardation and multiple congenital anomalies (MCA/MR). Screening for these chromosomal imbalances has mainly been done by standard karyotyping. Previous array CGH studies on selected patients with chromosomal phenotypes and normal karyotypes suggested an incidence of 10-15% of previously unnoticed de novo chromosomal imbalances.Objective: To report array CGH screening of a series of 140 patients (the largest published so far) with idiopathic MCA/MR but normal karyotype.Results: Submicroscopic chromosomal imbalances were detected in 28 of the 140 patients (20%) and included 18 deletions, seven duplications, and three unbalanced translocations. Seventeen of 24 imbalances were confirmed de novo and 19 were assumed to be causal. Excluding subtelomeric imbalances, our study identified 11 clinically relevant interstitial submicroscopic imbalances (8%). Taking this and previously reported studies into consideration, array CGH screening with a resolution of at least 1 Mb has been undertaken on 432 patients with MCA/MR. Most imbalances are non-recurrent and spread across the genome. In at least 8.8% of these patients (38 of 432) de novo intrachromosomal alterations have been identified.Conclusions: Array CGH should be considered an essential aspect of the genetic analysis of patients with MCA/MR. In addition, in the present study three patients were mosaic for a structural chromosome rearrangement. One of these patients had monosomy 7 in as few as 8% of the cells, showing that array CGH allows detection of low grade mosaicisims.