HECW2-related disorder in four Japanese patients
HECW2-related disorder in four Japanese patients
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DOI：
10.1002/ajmg.a.62363
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发表时间：
2021-05-28
影响因子：
2
通讯作者：
Yamamoto, Toshiyuki
中科院分区：
文献类型：
--
作者：
Yanagishita, Tomoe;Hirade, Takuya;Yamamoto, Toshiyuki
E3泛素蛋白连接酶2基因（HECW2）是一种具有HECT、C2和WW结构域的蛋白质泛素化酶。与蛋白质泛素化相关的几个基因与神经发育障碍有关。HECW2相关疾病已通过在患有张力减退、癫痫发作和语言缺失的神经发育障碍的患者中鉴定HECW2的新生变体而确立。最近，我们在4名日本神经发育障碍患者中发现了新的HECW2变异体。关于运动发育，其中两名患者不能行走，而另外两名患者由于肌张力减退而步态不稳。所有HECW2变体，包括先前报道的那些，都是错义的，并且没有鉴定出功能丧失的变体。大多数鉴定的变体位于HECT结构域周围。这些发现表明，HECT结构域周围的错义变体的显性负效应可能是HECW2相关疾病的潜在机制。
The HECT, C2, and WW domain containing E3 ubiquitin protein ligase 2 gene (HECW2) is involved in protein ubiquitination. Several genes associated with protein ubiquitination have been linked to neurodevelopmental disorders. HECW2-related disorder has been established through the identification of de novo variants in HECW2 in patients with neurodevelopmental disorders with hypotonia, seizures, and absent language. Recently, we identified novel HECW2 variants in four Japanese patients with neurodevelopmental disorders. Regarding motor development, two of the patients cannot walk, whereas the other two can walk with an unsteady gait, owing to hypotonia. All HECW2 variants, including those that were previously reported, are missense, and no loss-of-function variants have been identified. Most of the identified variants are located around the HECT domain. These findings suggest that the dominant negative effects of missense variants around the HECT domain may be the mechanism underlying HECW2-related disorder.