Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities
Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities
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DOI：
10.1016/j.ygeno.2007.10.011
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发表时间：
2008-02-01
期刊：
影响因子：
4.4
通讯作者：
Srivastava, Arland K.
中科院分区：
文献类型：
--
作者：
Griggs, Bradley L.;Ladd, Sydney;Srivastava, Arland K.
我们在两名无关的精神发育迟滞 (MR) 患者中发现了胞质分裂 8 基因贡献者 DOCK8 的破坏。在一名患有 MR 但无法言语的患者中，我们在亚端粒 9p 中绘制了约 230 kb 的基因组缺失。在第二名患者中，她是一位患有智力低下、外胚层发育不良和平衡易位的女性，t(X;9) (q13.1;p24)，我们将 9p24 断点映射到与 230-kb 亚端粒缺失的着丝粒末端重叠的区域。我们对关键 9p 缺失区域的 DOCKS 基因进行了表征，并确定两名患者中 DOCKS 基因的最长亚型均被截短。此外，DOCKS 基因在多种人体组织中表达，包括成人和胎儿的大脑。最近，有人提出 DOCKS 在影响丝状肌动蛋白组织的过程中的作用。影响肌动蛋白细胞骨架的几个基因与人类认知功能有关，因此 DOCKS 基因中的罕见突变可能导致某些常染色体显性智力低下病例。 (c) 2007 Elsevier Inc. 保留所有权利。
We have identified disruptions in the dedicator of cytokinesis 8 gene, DOCK8, in two unrelated patients with mental retardation (MR). In one patient, a mate with MR and no speech, we mapped a genomic deletion of approximately 230 kb in subtelomeric 9p. In the second patient, a female with mental retardation and ectodermal dysplasia and a balanced translocation, t(X;9) (q13. 1;p24), we mapped the 9p24 breakpoint to a region overlapping with the centromeric end of the 230-kb subtelomeric deletion. We characterized the DOCKS gene from the critical 9p deletion region and determined that the longest isoform of the DOCKS gene is truncated in both patients. Furthermore, the DOCKS gene is expressed in several human tissues, including adult and fetal brain. Recently, a role for DOCKS in processes that affect the organization of filamentous actin has been suggested. Several genes influencing the actin cytoskeleton have been implicated in human cognitive function and thus a possibility exists that the rare mutations in the DOCKS gene may contribute to some cases of autosomal dominant mental retardation. (c) 2007 Elsevier Inc. All rights reserved.