Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.
Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.
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DOI：
10.1136/jmg.2006.043166
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发表时间：
2006-11
影响因子：
4
通讯作者：
Philippe A
中科院分区：
文献类型：
--
作者：
Jacquemont ML;Sanlaville D;Redon R;Raoul O;Cormier-Daire V;Lyonnet S;Amiel J;Le Merrer M;Heron D;de Blois MC;Prieur M;Vekemans M;Carter NP;Munnich A;Colleaux L;Philippe A
自闭症谱系障碍（ASD）是指一组更广泛的神经生物学条件，广泛性发育障碍。他们的特点是一个症状三联体与社会互动的质的变化，沟通能力的缺陷，重复和刻板的兴趣和活动。ASD的患病率为每1000人中有1至3人。尽管有几个论点强烈的遗传贡献，大多数情况下的分子基础仍然无法解释。大约5%的自闭症患者有一个染色体异常可见细胞遗传学方法。最常见的是15 q11-q13重复，2 q37和22q13.3缺失。许多其他染色体不平衡已被描述。然而，其中大多数仍然无法使用常规核型分析检测，从而阻碍了诊断和遗传咨询。使用DNA微阵列研究了29例综合征型ASD患者，该DNA微阵列由基因组中间隔约1 Mb的大插入克隆构建。在8例（27.5%）患者中确定了8种临床相关重排：6种缺失和2种重复。改变的片段大小范围为1.4至16 Mb（2-19个克隆）。未发现复发性异常。这些结果清楚地表明，阵列比较基因组杂交应被认为是一个重要方面的综合征型ASD患者的遗传分析。此外，除了它们对诊断和遗传咨询的重要性外，它们可能允许描绘与ASD相关的新的连续基因综合征。最后，重排区域的详细分子分析可能为新的ASD基因的鉴定铺平道路。
Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11–q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling. 29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2–19 clones). No recurrent abnormality was identified. These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.
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影响因子：
3.1
作者：
Alsdorf, Rachel;Wyszynski, Diego F
通讯作者：
Wyszynski, Diego F
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
影响因子：
3.9
作者：
Gillberg, C
通讯作者：
Gillberg, C
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
4
作者：
Menten, B.;Maas, N.;Vermeesch, J. R.
通讯作者：
Vermeesch, J. R.