A novel variant in the transmembrane 4 domain of ANO3 identified in a two-year-old girl with developmental delay and tremor
A novel variant in the transmembrane 4 domain of ANO3 identified in a two-year-old girl with developmental delay and tremor
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在一名患有发育迟缓和震颤的两岁女孩中发现了 ANO3 跨膜 4 结构域的新变异
DOI：
10.1038/s10038-022-01082-5
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发表时间：
2022
影响因子：
3.5
通讯作者：
Kure Shigeo
中科院分区：
文献类型：
--
作者：
Aihara Yu;Shirota Matsuyuki;Kikuchi Atsuo;Katata Yu;Abe Yu;Niihori Tetsuya;Funayama Ryo;Nakayama Keiko;Aoki Yoko;Kure Shigeo
ANO 3编码Anoctamin-3，也称为TMEM 16 C，是一种钙激活的氯离子通道。ANO 3的杂合变体可引起肌张力障碍24，一种成人发病的局灶性肌张力障碍。一些儿科病例已被报道，但大多数患者智力正常，有一些例外。在此，我们报告一个两岁的小女孩，表现为轻度到中度的发育迟缓、震颤和共济失调步态，但没有明显的肌张力障碍。Trio外显子组测序鉴定了杂合的从头错义变体NM_031418.4：c.1809T>G，p.（Asn603Lys）。包括本例在内，已报告了3例ANO 3变异和智力残疾病例。预测这些变体在相同的α-螺旋（跨膜4结构域）上朝向相同的方向，表明这些变体与儿童期发作的运动障碍和智力残疾之间存在关联。在发育迟缓和运动障碍如震颤和共济失调的儿科病例中，ANO 3跨膜4结构域的特定变体可能是一个原因，即使在没有肌张力障碍的情况下。
ANO3encodes Anoctamin-3, also known as TMEM16C, a calcium-activated chloride channel. Heterozygous variants ofANO3can cause dystonia 24, an adult-onset focal dystonia. Some pediatric cases have been reported, but most patients were intellectually normal with some exceptions. Here, we report a two-year-old girl who showed mild to moderate developmental delay, tremor, and ataxic gait, but no obvious dystonia. Trio exome sequencing identified a heterozygous de novo missense variant NM_031418.4:c.1809T>G, p.(Asn603Lys) in theANO3gene. Three cases withANO3variants and intellectual disability have been reported, including the present case. These variants were predicted to face in the same direction on the same alpha-helix (the transmembrane 4 domain), suggesting an association between these variants and childhood-onset movement disorder with intellectual disability. In pediatric cases with developmental delay and movement disorders such as tremor and ataxia, specific variants in the transmembrane 4 domain ofANO3may be a cause, even in the absence of dystonia.