A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay
A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay
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DOI：
10.1016/j.braindev.2021.09.006
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发表时间：
2022-01-03
影响因子：
1.7
通讯作者：
Saitsu, Hirotomo
中科院分区：
文献类型：
--
作者：
Fukumura, Shinobu;Hiraide, Takuya;Saitsu, Hirotomo
背景：TMEM63A的杂合变异体最近被确定为婴儿发病的短暂性髓鞘炎的原因。迄今为止，在5例患者中报道了4种TMEM63A变异。这些患者表现出良好的临床过程、发育进展和髓鞘形成的完成。病例报告：患者是一名5岁的女孩，患有严重的整体发育迟缓，没有语言，没有翻身，没有凝视，张力低下，每日发作的自主神经发作。脑MRI显示深层和皮层下白质髓鞘化低，2个月大时t2加权成像呈高信号，4岁时无变化。患者及其父母的外显子组测序显示了一种新的从头错义变异，NM_014698.3:c。1658G>T, p.(Gly553Val)，在TMEM63A基因中，经Sanger测序证实。该变体尚未在公共数据库中登记，它替代了位于孔衬跨膜螺旋中的高度保守的甘氨酸残基。没有发现其他候选变异。结论：虽然TMEM63A变异体通常被认为会导致短暂性骨髓炎，并具有良好的发育进展，但在我们的患者中发现的一个新生TMEM63A变异体表明，TMEM63A相关的临床谱很广，包括严重的发育迟缓和癫痫发作。(c) 2021日本儿童神经病学学会。Elsevier B.V.版权所有。
Background: Heterozygous variants in TMEM63A have been recently identified as the cause of infantile-onset transient hypomyelination. To date, four TMEM63A variants have been reported in five patients. These patients exhibited favorable clinical course, developmental progress, and completion of myelination. Case report: The patient was a 5-year-old girl with severe global developmental delay, absent speech, no turning over, no gazing, hypotonia, and daily episodes of autonomic seizures. Brain MRI showed hypomyelination of deep and subcortical white matter that appeared hyperintense in T2-weighted imaging from 2 months of age and that showed no change at 4 years of age. Exome sequencing of the patient and her parents revealed a novel de novo missense variant, NM_014698.3:c.1658G>T, p.(Gly553Val), in the TMEM63A gene, which was confirmed by Sanger sequencing. The variant has not been registered in public databases, and it substitutes a highly conserved glycine residue located in a pore-lining transmembrane helix. No other candidate variants were identified. Conclusions: Although TMEM63A variants are generally thought to cause transient hypomyelination with favorable developmental progress, identification of a de novo TMEM63A variant in our patient suggests that the TMEM63A-related clinical spectrum is broad and includes severe developmental delay with seizures. (c) 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.