Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
复制标题
DOI：
10.1093/hmg/ddr243
复制
发表时间：
2011-09-01
影响因子：
3.5
通讯作者：
Zoghbi HY
中科院分区：
文献类型：
--
作者：
Schaaf CP;Sabo A;Sakai Y;Crosby J;Muzny D;Hawes A;Lewis L;Akbar H;Varghese R;Boerwinkle E;Gibbs RA;Zoghbi HY
自闭症谱系障碍（ASD）是一组异质性的神经发育障碍。虽然在识别与综合征型自闭症相关的基因和拷贝数变异方面取得了重大进展，但迄今为止对特发性非综合征型自闭症的病因知之甚少。桑格测序的21个已知的自闭症易感基因在339个高功能，特发性ASD的个人揭示了从头突变，在这些基因中的至少一个在6 339先证者（1.8%）。此外，观察到多个寡基因杂合性事件，影响339个先证者中的23个（6.8%）。通过相同的测序技术筛选CACNA1C、CDKL5、HOXA 1、SHANK 3、TSC 1、TSC 2和UBE 3A的新编码变体的对照人群显示，对照组是显著（P < 0.01）较低的寡基因杂合事件的携带者，这表明寡基因杂合性是ASD发病的新的潜在机制。
Autism spectrum disorders (ASDs) are a heterogeneous group of neuro-developmental disorders. While significant progress has been made in the identification of genes and copy number variants associated with syndromic autism, little is known to date about the etiology of idiopathic non-syndromic autism. Sanger sequencing of 21 known autism susceptibility genes in 339 individuals with high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of 339 probands (1.8%). Additionally, multiple events of oligogenic heterozygosity were seen, affecting 23 of 339 probands (6.8%). Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1, TSC2 and UBE3A by the same sequencing technology revealed that controls were carriers of oligogenic heterozygous events at significantly (P < 0.01) lower rate, suggesting oligogenic heterozygosity as a new potential mechanism in the pathogenesis of ASDs.
登录
查看更多内容
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：
10.6
作者：
Constantino, JN;Todd, RD
通讯作者：
Todd, RD
影响因子：
9.8
作者：
Laumonnier, F;Bonnet-Brilhault, F;Briault, S
通讯作者：
Briault, S
影响因子：
9.8
作者：
Newbury, DF;Bonora, E;Monaco, AP
通讯作者：
Monaco, AP
DOI：
10.1016/j.psc.2009.12.002
发表时间：
2010-03
期刊：
The Psychiatric clinics of North America
影响因子：
--
作者：
El-Fishawy P;State MW
通讯作者：
State MW