Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability.
Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability.
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DOI：
10.1136/jmg.2010.079426
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发表时间：
2011-01
影响因子：
4
通讯作者：
Monaco AP
中科院分区：
文献类型：
--
作者：
Pagnamenta AT;Khan H;Walker S;Gerrelli D;Wing K;Bonaglia MC;Giorda R;Berney T;Mani E;Molteni M;Pinto D;Le Couteur A;Hallmayer J;Sutcliffe JS;Szatmari P;Paterson AD;Scherer SW;Vieland VJ;Monaco AP
自闭症谱系障碍（ASD）的特征是社交障碍和重复行为模式，学习障碍（LD）通常在高达70%的病例中出现。最近的一项研究使用PPL统计框架确定了染色体16 q21上的一个新的遗传连锁区域，该区域仅限于患有LD的ASD家族。在这项研究中，两个家庭与孤独症和/或LD的海港罕见的>1.6 Mb微缺失位于这个连锁区。 以碱基对分辨率绘制缺失断点，并使用1 M单核苷酸多态性（SNP）技术、阵列比较基因组杂交（CGH）、长距离PCR和桑格测序的组合进行分离分析。通过分析已发表的SNP阵列数据来确定对照受试者中相似基因组变体的频率。使用逆转录酶PCR和9周人胚胎的原位杂交分析来评估CDH 8的表达，CDH 8是被这些微缺失破坏的唯一基因。 chr 16：60 025 584-61 667 839的缺失从他们未受影响的母亲传递到三个患有自闭症和LD的男孩中的三个，以及四个未受影响的兄弟姐妹中的一个。 在第二个家庭中，一个重叠删除的chr 16：58 724 527-60 547 472被传递到一个人与严重的LD从他的父亲与中度LD。 在5023个对照中未观察到破坏CDH 8的拷贝数变异（CNV）。表达分析表明，这两种CDH 8亚型存在于发育中的人类皮质中。罕见的家族性16 q21微缺失和表达分析表明CDH 8与自闭症和LD的易感性有关。
Autism spectrum disorder (ASD) is characterised by impairments in social communication and by a pattern of repetitive behaviours, with learning disability (LD) typically seen in up to 70% of cases. A recent study using the PPL statistical framework identified a novel region of genetic linkage on chromosome 16q21 that is limited to ASD families with LD. In this study, two families with autism and/or LD are described which harbour rare >1.6 Mb microdeletions located within this linkage region. The deletion breakpoints are mapped at base-pair resolution and segregation analysis is performed using a combination of 1M single nucleotide polymorphism (SNP) technology, array comparative genomic hybridisation (CGH), long-range PCR, and Sanger sequencing. The frequency of similar genomic variants in control subjects is determined through analysis of published SNP array data. Expression of CDH8, the only gene disrupted by these microdeletions, is assessed using reverse transcriptase PCR and in situ hybridisation analysis of 9 week human embryos. The deletion of chr16: 60 025 584–61 667 839 was transmitted to three of three boys with autism and LD and none of four unaffected siblings, from their unaffected mother. In a second family, an overlapping deletion of chr16: 58 724 527–60 547 472 was transmitted to an individual with severe LD from his father with moderate LD. No copy number variations (CNVs) disrupting CDH8 were observed in 5023 controls. Expression analysis indicates that the two CDH8 isoforms are present in the developing human cortex. Rare familial 16q21 microdeletions and expression analysis implicate CDH8 in susceptibility to autism and LD.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
9.8
作者：
Bhalla, Kavita;Luo, Yue;Srivastava, Anand K.
通讯作者：
Srivastava, Anand K.
影响因子：
7
作者：
Shaikh, Tamim H.;Gai, Xiaowu;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
DOI：
10.1002/ajmg.1497
发表时间：
2001-08-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Bradford, Y;Haines, J;Piven, J
通讯作者：
Piven, J