Iourov Ivan Y, Vorsanova Svetlana G, Kurinnaia Oxana S, Zelenova Maria A, Silvanovich Alexandra P, Yurov Yuri B
Mental Health Research Center, Russian Academy of Medical Sciences, 119152, Moscow, Russia.
Mol Cytogenet. 2012 Dec 31;5(1):46. doi: 10.1186/1755-8166-5-46.
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
背景：阵列比较基因组杂交（CGH）已被反复证明是识别临床人群基因组变异的成功工具。在过去十年中，阵列CGH的应用已导致在神经精神（神经行为）疾病中发现新的致病性亚微观染色体失衡和拷贝数变异（CNV）。目前，基于阵列CGH的技术已成为神经精神疾病患者以及智力残疾（智力发育迟缓）和先天性异常儿童分子诊断和研究的一个组成部分。在此，我们介绍通过BAC阵列CGH分析的俄罗斯智力残疾、自闭症、癫痫和先天性异常儿童队列以及一种新的生物信息学策略。 结果：在根据临床标准以及分子和细胞遗传学数据从2426例患者（2007年11月至2012年5月期间进行了细胞遗传学和分子评估）中高度筛选出的54例个体中，26例（48%）检测到染色体失衡。在两名患者（4%）中，观察到一种先前未描述的情况。后者被指定为减数分裂（构成性）基因组不稳定，导致多个亚微观重排（包括CNV）。使用生物信息学策略，我们能够在15例个体（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例染色体失衡中有8例（31%）此前未被报道。其中，3例为9号和21号染色体细微缺失同时出现。 结论：我们对患有智力残疾、自闭症、癫痫和先天性异常的俄罗斯患者进行了阵列CGH研究。总的来说，发现临床相关基因组变异的表型表现是由影响12,47个致病和参与通路的基因的基因组重排引起的。显然，其中只有一小部分是智力残疾、自闭症或癫痫的真正候选基因。我们初步的阵列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。
Open Access Maced J Med Sci. 2017-7-27
BMC Genomics. 2016-10-17
BMC Med Genet. 2016-11-25
Intractable Rare Dis Res. 2023-5
Mol Cytogenet. 2023-1-5
Mol Cytogenet. 2022-8-19
Mol Genet Genomic Med. 2022-8
Mol Cytogenet. 2018-12-24
Eur J Med Genet. 2012-12
Korean J Pediatr. 2012-3
Eur J Hum Genet. 2011-4-20
Curr Genomics. 2010-9
Curr Genomics. 2010-9
Zotero 插件