Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.
Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.
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DOI：
10.1136/jmg.2008.059907
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发表时间：
2009-04
影响因子：
4
通讯作者：
Wu BL
中科院分区：
文献类型：
--
作者：
Miller DT;Shen Y;Weiss LA;Korn J;Anselm I;Bridgemohan C;Cox GF;Dickinson H;Gentile J;Harris DJ;Hegde V;Hundley R;Khwaja O;Kothare S;Luedke C;Nasir R;Poduri A;Prasad K;Raffalli P;Reinhard A;Smith SE;Sobeih MM;Soul JS;Stoler J;Takeoka M;Tan WH;Thakuria J;Wolff R;Yusupov R;Gusella JF;Daly MJ;Wu BL
染色体15q13.2q13.3断点（BP4-BP5）片段重复介导与智力低下、癫痫和/或脑电图异常相关的复发性基因组失衡综合征。来自1445名不相关患者的DNA样本连续提交到波士顿儿童医院进行临床阵列比较基因组杂交（CGH）测试，以及来自自闭症遗传资源交换（AGRE）存储库中751个家庭的1441名自闭症患者的DNA样本。我们报告了5例BP4-BP5缺失患者的临床特征，3例BP4-BP5重复，2例通过全基因组高分辨率寡核苷酸阵列CGH鉴定出重叠但较小的重复。这些BP4-BP5缺失的病例表现出轻微的畸形特征，显著的表达性语言缺陷，以及一系列神经精神障碍，包括自闭症谱系障碍、多动症、焦虑症和情绪障碍。认知障碍从中度智力迟钝到智力正常并伴有学习障碍。BP4-BP5全长约1.5Mb (chr15:28.719-30.298Mb)，包含6个内参基因和1个miRNA基因，较小的复制全长约500 kb (chr15:28.902-29.404 Mb)，包含3个内参基因和1个miRNA基因。BP4-BP5缺失和重复事件跨越了CHRNA7，一个癫痫的候选基因。然而，这里报告的这些人都没有癫痫，尽管有两个脑电图异常。染色体15q13.2q13.3 BP4-BP5微缺失/重复综合征的表型可能包括自闭症谱系障碍、各种神经精神障碍和认知障碍的特征。认识到这种更广泛的表型对临床诊断测试和努力了解该综合征的潜在病因具有重要意义。
Segmental duplications at breakpoints (BP4–BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or EEG abnormalities. DNA samples from 1,445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children’s Hospital Boston and DNA samples from 1,441 individuals with Autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4–BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4–BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, ADHD, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4–BP5 covers ~1.5Mb (chr15:28.719–30.298Mb) and includes 6 reference genes and 1 miRNA gene, while the smaller duplications cover ~500 kb (chr15:28.902–29.404 Mb) and contain 3 reference genes and one miRNA gene. The BP4–BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. The phenotype of chromosome 15q13.2q13.3 BP4–BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying etiology of this syndrome.
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影响因子：
9.8
作者：
Browne, CE;Dennis, NR;Barber, JCK
通讯作者：
Barber, JCK
DOI：
10.1002/ajmg.b.30306
发表时间：
2006-09-05
影响因子：
2.8
作者：
Flomen, Rachel H.;Collier, David A.;Makoff, Andrew J.
通讯作者：
Makoff, Andrew J.
影响因子：
11
作者：
Meyer, J;Ortega, G;Lesch, KP
通讯作者：
Lesch, KP
影响因子：
4.5
作者：
Fan, Jin-Bo;Ma, Jie;He, Lin
通讯作者：
He, Lin
影响因子：
3.5
作者：
Elmslie, FV;Rees, M;Gardiner, RM
通讯作者：
Gardiner, RM