一名男性自闭症患者存在一条涉及 6 号、10 号和 21 号染色体的复杂重排，其 21q21.1-q21.3 区域发生了一个 8.8Mb 的从头缺失。
A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex rearrangement involving chromosomes 6, 10, and 21.
机构信息
Division of Human Genetics, The Children's Hospital of Philadelphia, 1002 ARC, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
出版信息
Am J Med Genet A. 2010 Jan;152A(1):196-202. doi: 10.1002/ajmg.a.33176.
Abstract
We report here on a normal-appearing male with pervasive developmental disorder who was found to have a de novo, apparently balanced complex rearrangement involving chromosomes 6, 10, and 21: 46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.2). Further analysis by high-density oligonucleotide microarray was performed, showing an 8.8-Mb heterozygous deletion at 21q21.1-q21.3. Interestingly, the deletion is distal to the translocation breakpoint on chromosome 21. The deletion involves 19 genes, including NCAM2 and GRIK1, both of which are associated with normal brain development and function, and have been considered as possible candidate genes in autism and other neurobehavioral disorders. This case underscores the utility of genomewide microarray analysis for the detection of copy number alterations in patients with apparently balanced complex rearrangements and abnormal phenotypes.
摘要
我们在此报告一例表型正常的男性患者，患有广泛发育障碍，经检测发现其存在一个新发的、明显平衡的复杂重排，涉及染色体 6、10 和 21：46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.2)。进一步通过高密度寡核苷酸微阵列分析，显示 21q21.1-q21.3 存在一个 8.8Mb 的杂合性缺失。有趣的是，该缺失位于染色体 21 的易位断点远端。该缺失涉及 19 个基因，包括与正常大脑发育和功能相关的 NCAM2 和 GRIK1，它们都被认为是自闭症和其他神经行为障碍的候选基因。该病例强调了全基因组微阵列分析在检测具有明显平衡复杂重排和异常表型的患者拷贝数改变方面的效用。
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本文引用的文献
1
Mechanisms for human genomic rearrangements.人类基因组重排的机制。
Pathogenetics. 2008 Nov 3;1(1):4. doi: 10.1186/1755-8417-1-4.
2
A de novo 6p interstitial deletion and a complex translocation involving chromosomes 2, 6, and 14 in a mildly developmentally delayed patient.一名轻度发育迟缓患者存在6号染色体短臂间质性缺失以及涉及2号、6号和14号染色体的复杂易位。
Am J Med Genet A. 2008 Dec 15;146A(24):3230-3. doi: 10.1002/ajmg.a.32582.
3
Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype.新发或家族性明显平衡易位且伴有异常表型患者的隐匿性基因组失衡
Mol Cytogenet. 2008 Jul 21;1:15. doi: 10.1186/1755-8166-1-15.
4
Presynaptic glutamate receptors: physiological functions and mechanisms of action.突触前谷氨酸受体：生理功能与作用机制
Nat Rev Neurosci. 2008 Jun;9(6):423-36. doi: 10.1038/nrn2379. Epub 2008 May 9.
5
Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia.离子型谷氨酸受体mRNA在人类丘脑的表达：精神分裂症患者无变化
Brain Res. 2008 Jun 12;1214:23-34. doi: 10.1016/j.brainres.2008.03.039. Epub 2008 Apr 1.
6
Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder.在自闭症谱系障碍中检测到的新型亚显微染色体异常。
Biol Psychiatry. 2008 Jun 15;63(12):1111-7. doi: 10.1016/j.biopsych.2008.01.009. Epub 2008 Mar 28.
7
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Am J Hum Genet. 2008 Apr;82(4):916-26. doi: 10.1016/j.ajhg.2008.02.007. Epub 2008 Mar 27.
8
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Am J Hum Genet. 2008 Apr;82(4):927-36. doi: 10.1016/j.ajhg.2008.02.012. Epub 2008 Mar 27.
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