Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations
Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations
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DOI：
10.1136/jmg.2005.036913
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Bacino, C. A.
中科院分区：
文献类型：
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作者：
Sahoo, T.;Peters, S. U.;Bacino, C. A.
背景资料：Angelman综合征（AS）是一种神经发育障碍，其特征是严重的精神发育迟滞、畸形特征、共济失调、癫痫发作和典型的行为特征，包括快乐的社交倾向。AS是由位于染色体15 q11-q13上的印记区域的UBE 3A（E6相关蛋白泛素蛋白连接酶3A基因）的母体缺陷引起的。虽然AS有四种不同的分子类型，但15 q11-q13区域的缺失约占70%的AS患者。这些缺失通常通过荧光原位杂交研究来检测。缺失也可以根据其大小分为I类和II类，前者更大，包括后者。方法：我们研究了22例AS患者由于微缺失使用基于微阵列的比较基因组杂交（阵列CGH）测定来定义缺失并分析其表型严重性，特别是自闭症表型的表达，以建立临床相关性。总体而言，与较小的II类缺失儿童相比，较大的I类缺失儿童更有可能符合自闭症标准，认知得分较低，表达语言得分较低。I类缺失的儿童也需要更多的药物来控制他们的癫痫发作比那些在II类group.Conclusions：有四个已知的基因（NIPA 1，NIPA 2，CYFIP 1，和GCP 5），是受I类，但不是II类缺失，从而提高了这些基因在自闭症中的作用的可能性，以及表达语言技能的发展。
Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterised by severe mental retardation, dysmorphic features, ataxia, seizures, and typical behavioural characteristics, including a happy sociable disposition. AS is caused by maternal deficiency of UBE3A (E6 associated protein ubiquitin protein ligase 3A gene), located in an imprinted region on chromosome 15q11-q13. Although there are four different molecular types of AS, deletions of the 15q11-q13 region account for approximately 70% of the AS patients. These deletions are usually detected by fluorescence in situ hybridisation studies. The deletions can also be subclassified based on their size into class I and class II, with the former being larger and encompassing the latter.Methods: We studied 22 patients with AS due to microdeletions using a microarray based comparative genomic hybridisation ( array CGH) assay to define the deletions and analysed their phenotypic severity, especially expression of the autism phenotype, in order to establish clinical correlations.Results: Overall, children with larger, class I deletions were significantly more likely to meet criteria for autism, had lower cognitive scores, and lower expressive language scores compared with children with smaller, class II deletions. Children with class I deletions also required more medications to control their seizures than did those in the class II group.Conclusions: There are four known genes (NIPA1, NIPA2, CYFIP1, & GCP5) that are affected by class I but not class II deletions, thus raising the possibility of a role for these genes in autism as well as the development of expressive language skills.