Identification of causative genes for reading disability in Williams syndrome

威廉姆斯综合征阅读障碍致病基因的鉴定

• 批准号: 21791005
• 负责人: YAGIHASHI Tatsuhiko
• 金额: $ 2.16万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791005/
• 关键词: Williams症候群; マイクロアレイ; 認知機能障害; 遺伝子型-表現型相関; 遺伝子; 認知科学; 読字障害

Williams syndrome (WS) is a genomic disorder caused by a hemizygous deletion of contiguous genes on chromosome 7q11.23. WS clinically shows cardiovascular abnormalities, typical facial features, and cognitive dysfunction. Most patients with WS have similar deletions of approximately 1.4 to 1.6Mb at WS region, however a few exceptional cases with larger deletions have been reported. The aim of this study was to investigate the individual contribution of genes to WS specific neurocognitive profile by genotype-phenotype correlations analysis. An array comparative genomic hybridization (array CGH) analysis revealed that one patient had a three times larger deletion (4.2 Mb) than the typical deletion at WS region. The developmental quotient of the patients with the 4.2 Mb deletion was significantly lower (DQ : 14) than those with the typical deletions (mean : 48.8). Deleted genes in the 4.2 Mb deletion include HSPB1 coding Heat Shock Protein 27. Severe developmental delay observed in the presently reported patient might be partly accounted for by a hemizygous deletion of HSPB1 in that HSPB1 helps protect neural cells under various adverse conditions. Array CGH analysis for detection of deleted genes may allow us to further estimate the severity of phenotype.

威廉姆斯综合征（WS）是由染色体7q11.23上的相邻基因的半合子缺失引起的基因组疾病。WS临床表现为心血管异常、典型的面部特征和认知功能障碍。大多数WS患者在WS区域有大约1.4至1.6Mb的类似缺失，但也有少数例外病例报告有较大的缺失。本研究的目的是通过基因型-表型相关分析来研究WS特异性神经认知功能的基因个体贡献。阵列比较基因组杂交（阵列CGH）分析显示，一个病人有三倍大的缺失（4.2 Mb）比典型的缺失在WS区域。4.2Mb缺失组发育商（DQ：14）明显低于典型缺失组（平均值：48.8）。在4.2 Mb缺失中的HSPB 1基因包括编码热休克蛋白27的HSPB 1。在目前报道的患者中观察到的严重发育迟缓可能部分归因于HSPB 1的半合子缺失，因为HSPB 1有助于在各种不利条件下保护神经细胞。阵列CGH分析检测缺失基因可使我们进一步估计表型的严重程度。

项目成果

視空間認知障害をもつ児のコンピューター学習支援～ウイリアムズ症候群をモデルとして

对视觉空间认知障碍儿童的计算机学习支持——以威廉姆斯综合征为模型

• 发表时间: 2011
• 作者: 柳橋達彦;小崎健次郎;高橋孝雄
• 通讯作者: 高橋孝雄