An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism
An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism
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DOI：
10.1136/jmg.2006.044537
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
McInnes, L. Alison
中科院分区：
文献类型：
--
作者：
Edelmann, Lisa;Prosnitz, Aaron;McInnes, L. Alison
背景：在一项自闭症的遗传研究中，我们检查了一名符合自闭症谱系障碍诊断标准的女童，但同时也表现出与Williams-Beuren综合征（WBS）相关的认知-行为特征（CBP）。WBS CBP包括视觉空间能力受损、过于友好的性格、过度的非社交焦虑和语言迟缓。方法：采用基于阵列的比较基因组杂交（aCGH）技术，检测WBS缺失区间远端对应BAC RP11-89A20的缺失。采用荧光原位杂交法确定半合子性，采用定量聚合酶链反应测定基因组DNA拷贝数进行精细定位。结果：GTF2IRD1的近端断点定位于内含子1，远端断点位于端粒处2.4-3.1 Mb。GTF2I主题完全半合,通常在运营商删除经典的类似于1.5 Mb WBS删除和GTF2IRD2,删除在运营商的罕见的类似于1.84 Mb WBS删除。结论：GTF2转录因子家族的半合子性足以产生WBS CBP的许多方面，特别是GTF2转录因子在视觉空间构建缺陷中的作用。在这种情况下，自闭症的症状可能是由于典型WBS间隔之外的其他基因缺失或对其他位点基因表达的远程影响。
Background: During a genetic study of autism, a female child who met diagnostic criteria for autism spectrum disorder, but also exhibited the cognitive-behavioural profile (CBP) associated with Williams-Beuren syndrome (WBS) was examined. The WBS CBP includes impaired visuospatial ability, an overly friendly personality, excessive non-social anxiety and language delay.Methods: Using array-based comparative genomic hybridisation (aCGH), a deletion corresponding to BAC RP11-89A20 in the distal end of the WBS deletion interval was detected. Hemizygosity was confirmed using fluorescence in situ hybridisation and fine mapping was performed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction.Results: The proximal breakpoint was mapped to intron 1 of GTF2IRD1 and the distal breakpoint lies 2.4-3.1 Mb towards the telomere. The subject was completely hemizygous for GTF2I, commonly deleted in carriers of the classic similar to 1.5 Mb WBS deletion, and GTF2IRD2, deleted in carriers of the rare similar to 1.84 Mb WBS deletion.Conclusion: Hemizygosity of the GTF2 family of transcription factors is sufficient to produce many aspects of the WBS CBP, and particularly implicate the GTF2 transcription factors in the visuospatial construction deficit. Symptoms of autism in this case may be due to deletion of additional genes outside the typical WBS interval or remote effects on gene expression at other loci.