Zebrafish Gene Knockdowns Imply Roles for Human YWHAG in Infantile Spasms and Cardiomegaly
Zebrafish Gene Knockdowns Imply Roles for Human YWHAG in Infantile Spasms and Cardiomegaly
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DOI：
10.1002/dvg.20607
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发表时间：
2010-04-01
期刊：
影响因子：
1.5
通讯作者：
Yamamoto, Toshiyuki
中科院分区：
文献类型：
--
作者：
Komoike, Yuta;Fujii, Katsunori;Yamamoto, Toshiyuki
Williams-Beuren综合征（WBS）是一种神经发育障碍，表现为小精灵样脸、瓣上主动脉狭窄、特定的认知行为特征和婴儿高钙血症。我们遇到了两个WBS患者表现为婴儿痉挛，这在WBS中是非常罕见的。阵列比较基因组杂交（aCGH）和荧光原位杂交（FISH）分析显示，两例患者在7q11.23位点存在非典型的5.7 mb和4.1 mb缺失，包括WBS关键区域，并分别扩展到近端和端粒侧。在近端，AUTS2和CALN1可能有助于表型。在端粒侧，有两个候选基因HIP1和YWHAG。由于无法获得它们的详细信息，我们利用斑马鱼基因敲低来研究它们的功能。当斑马鱼的ywhag1基因被敲除时，我们观察到斑马鱼的脑体积减小，心管直径增大，这表明端粒缺失患者的婴儿痉挛和心脏增大可能是由于YWHAG的单倍不足引起的。创世纪48:233 - 243,2010。(C) 2010 Wiley-Liss, Inc。
Williams-Beuren syndrome (WBS) is a neuro-developmental disorder presenting with an elfin-like face, supravalvular aortic stenosis, a specific cognitive-behavioral profile, and infantile hypercalcemia. We encountered two WBS patients presenting with infantile spasms, which is extremely rare in WBS. Array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) analyses revealed atypical 5.7-Mb and 4.1-Mb deletions at 7q11.23 in the two patients, including the WBS critical region and expanding into the proximal side and the telomeric side, respectively. On the proximal side, AUTS2 and CALN1 may contribute to the phenotype. On the telomeric side, there are two candidate genes HIP1 and YWHAG. Because detailed information of them was unavailable, we investigated their functions using gene knockdowns of zebrafish. When zebrafish ywhag1 was knocked down, reduced brain size and increased diameter of the heart tube were observed, indicating that the infantile spasms and cardiomegaly seen in the patient with the telomeric deletion may be derived from haploinsufficiency of YWHAG. genesis 48:233-243,2010. (C) 2010 Wiley-Liss, Inc.