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Fukumura S, Hiraide T, Yamamoto A, et al. A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay. Brain Dev. 2021;44(2):178-183doi: 10.1016/j.braindev.2021.09.006.
Fukumura, S., Hiraide, T., Yamamoto, A., Tsuchida, K., Aoto, K., Nakashima, M., & Saitsu, H. (2022). A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay. Brain & development, 44(2), 178-183. https://doi.org/10.1016/j.braindev.2021.09.006
Fukumura, Shinobu, et al. "A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay." Brain & development vol. 44,2 (2022): 178-183. doi: https://doi.org/10.1016/j.braindev.2021.09.006
Fukumura S, Hiraide T, Yamamoto A, Tsuchida K, Aoto K, Nakashima M, Saitsu H. A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay. Brain Dev. 2022 Feb;44(2):178-183. doi: 10.1016/j.braindev.2021.09.006. Epub 2021 Sep 28. PMID: 34598833.
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Brain Dev. 2022 Feb;44(2):178-183. doi: 10.1016/j.braindev.2021.09.006. Epub 2021 Sep 28.

A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay.

Brain & development

Shinobu Fukumura, Takuya Hiraide, Akiyo Yamamoto, Kousuke Tsuchida, Kazushi Aoto, Mitsuko Nakashima, Hirotomo Saitsu

Affiliations

  1. Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: [email protected].
  2. Biochemistry Department, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  3. Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.

PMID: 34598833 DOI: 10.1016/j.braindev.2021.09.006

Abstract

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.

Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Keywords: Global developmental delay; Hypomyelinating leukodystrophy; Severe hypomyelination; TMEM63A

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