A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies
A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies
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DOI：
10.1038/s10038-021-00953-7
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发表时间：
2021-06-25
影响因子：
3.5
通讯作者：
Saitsu，Hirotomo
中科院分区：
文献类型：
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作者：
Miyamoto，Sachiko;Kato，Mitsuhiro;Saitsu，Hirotomo
脑畸形具有异质性遗传背景。微管蛋白病是由微管蛋白和微管相关基因的变体引起的广泛的脑畸形。最近报道了来自7个具有发育迟缓、智力残疾和脑畸形的家族的11名患者中的TTC5（也称为p300的应激反应激活剂）的双等位基因变体。在这里，我们报告了一个日本男孩的TTC 5复合杂合移码变异，他表现出严重的精神发育迟缓和假性延髓麻痹伴生长障碍。脑磁共振成像显示简化的脑回模式和不可检测的内囊前肢，提示微管蛋白病。结果表明，Ttc 5基因在Neuro2a细胞中表达下调，Tubulin β3蛋白水平降低，细胞周期异常。我们的报告提示TTC5相关的脑畸形和微管蛋白病之间可能存在联系。
Brain malformations have heterogeneous genetic backgrounds. Tubulinopathies are a wide range of brain malformations caused by variants in tubulin and microtubules-associated genes. Recently biallelic variants inTTC5, also known as stress responsive activator of p300, have been reported in 11 patients from seven families with developmental delay, intellectual disability, and brain malformations. Here, we report compound heterozygous frameshift variants inTTC5in a Japanese boy who showed severe psychomotor developmental delay and pseudobulbar palsy with growth failure. Brain magnetic resonance imaging showed a simplified gyral pattern and undetectable anterior limb of the internal capsule, suggesting tubulinopathies. Immunoblotting using lymphoblastoid cells derived from the patient showed undetectable TTC5 protein.Ttc5silencing by RNA interference in Neuro2a cells reduced Tubulin β3 protein level and caused abnormal cell cycle. Our report suggests a possible link betweenTTC5-related brain malformation and tubulinopathies.