Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies.
Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies.
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DOI：
10.1186/1755-8166-5-46
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发表时间：
2012-12-31
影响因子：
1.3
通讯作者：
Yurov YB
中科院分区：
文献类型：
--
作者：
Iourov IY;Vorsanova SG;Kurinnaia OS;Zelenova MA;Silvanovich AP;Yurov YB
阵列比较基因组杂交 (CGH) 已被多次证明是鉴定临床人群基因组变异的成功工具。在过去的十年中，阵列 CGH 的实施已导致神经精神（神经行为）疾病中新的致病亚显微染色体失衡和拷贝数变异 (CNV) 的识别。目前，基于阵列 CGH 的技术已成为神经精神疾病个体以及智力障碍（精神发育迟滞）和先天性异常儿童分子诊断和研究的重要组成部分。在这里，我们介绍了通过 BAC 阵列 CGH 和新颖的生物信息学策略分析的俄罗斯智力障碍、自闭症、癫痫和先天性异常儿童队列。根据临床标准以及分子和细胞遗传学数据精心挑选的 54 名个体（2007 年 11 月至 2012 年 5 月期间对 2426 名患者进行了细胞遗传学和分子学评估）中，有 26 名个体（48%）检测到染色体失衡。在两名患者 (4%) 中，观察到了先前未描述的情况。后者被认为是减数分裂（组成性）基因组不稳定性导致多种亚显微重排（包括 CNV）。使用生物信息学策略，我们能够在 15 名个体 (28%) 中识别出临床相关的 CNV。选定的病例通过分子细胞遗传学和分子遗传学方法得到证实。 26 种染色体失衡中有 8 种 (31%) 以前未曾报道过。其中，3例为9号和21号染色体细微缺失同时发生。我们对患有智力障碍、自闭症、癫痫和先天性异常的俄罗斯患者进行了一系列 CGH 研究。总的来说，临床相关基因组变异的表型表现是由影响 1247 个致病基因和通路相关基因的基因组重排引起的。显然，他们中真正患有智力障碍、自闭症或癫痫症的人要少得多。我们初步阵列 CGH 和生物信息学研究的成功使我们能够扩大队列。根据现有文献，这是对俄罗斯神经精神疾病和先天性异常儿童队列的首次全面阵列 CGH 评估。
Array comparative genomic hybridization (CGH) has been repeatedly shown to be a successful tool for the identification of genomic variations in a clinical population. During the last decade, the implementation of array CGH has resulted in the identification of new causative submicroscopic chromosome imbalances and copy number variations (CNVs) in neuropsychiatric (neurobehavioral) diseases. Currently, array-CGH-based technologies have become an integral part of molecular diagnosis and research in individuals with neuropsychiatric disorders and children with intellectual disability (mental retardation) and congenital anomalies. Here, we introduce the Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies analyzed by BAC array CGH and a novel bioinformatic strategy. Among 54 individuals highly selected according to clinical criteria and molecular and cytogenetic data (from 2426 patients evaluated cytogenetically and molecularly between November 2007 and May 2012), chromosomal imbalances were detected in 26 individuals (48%). In two patients (4%), a previously undescribed condition was observed. The latter has been designated as meiotic (constitutional) genomic instability resulted in multiple submicroscopic rearrangements (including CNVs). Using bioinformatic strategy, we were able to identify clinically relevant CNVs in 15 individuals (28%). Selected cases were confirmed by molecular cytogenetic and molecular genetic methods. Eight out of 26 chromosomal imbalances (31%) have not been previously reported. Among them, three cases were co-occurrence of subtle chromosome 9 and 21 deletions. We conducted an array CGH study of Russian patients suffering from intellectual disability, autism, epilepsy and congenital anomalies. In total, phenotypic manifestations of clinically relevant genomic variations were found to result from genomic rearrangements affecting 1247 disease-causing and pathway-involved genes. Obviously, a significantly lesser part of them are true candidates for intellectual disability, autism or epilepsy. The success of our preliminary array CGH and bioinformatic study allows us to expand the cohort. According to the available literature, this is the first comprehensive array CGH evaluation of a Russian cohort of children with neuropsychiatric disorders and congenital anomalies.
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影响因子：
5.2
作者：
Mitter, Diana;Ullmann, Reinhard;Lohmann, Dietmar
通讯作者：
Lohmann, Dietmar
影响因子：
4
作者：
Rehnström, K;Ylisaukko-oja, T;Järvelä, I
通讯作者：
Järvelä, I
影响因子：
1.9
作者：
Hansson, Kerstin B. M.;Gijsbers, Antoinet C. J.;Kant, Sarina G.
通讯作者：
Kant, Sarina G.
影响因子：
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作者：
Park, Ji Hyeon;Woo, Jung Hoon;Cha, Dong Hyun
通讯作者：
Cha, Dong Hyun
健康和疾病的体细胞基因组变异。
影响因子：
2.6
作者：
Iourov IY;Vorsanova SG;Yurov YB
通讯作者：
Yurov YB