A TUBB4A Met363Thr variant in pediatric hypomyelination without atrophy of the basal ganglia

Marina Hashiguchi; Yukifumi Monden; Yasuyuki Nozaki; Kazuki Watanabe; Mitsuko Nakashima; Hirotomo Saitsu; Takanori Yamagata; Hitoshi Osaka

doi:10.1038/s41439-022-00198-6

A TUBB4A Met363Thr variant in pediatric hypomyelination without atrophy of the basal ganglia

Hum Genome Var. 2022 Jun 3;9(1):19. doi: 10.1038/s41439-022-00198-6.

Authors

Marina Hashiguchi¹, Yukifumi Monden², Yasuyuki Nozaki^{1

3}, Kazuki Watanabe⁴, Mitsuko Nakashima⁴, Hirotomo Saitsu⁴, Takanori Yamagata¹, Hitoshi Osaka¹

Affiliations

¹ Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
² Department of Pediatrics, Jichi Medical University, Tochigi, Japan. mon4441977319@jichi.ac.jp.
³ Department of Pediatrics, Shin-Oyama City Hospital, Tochigi, Japan.
⁴ Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, Japan.

Abstract

TUBB4A gene variants cause dystonia type 4 and hypomyelination with atrophy of the basal ganglia and cerebellum. We report the case of a child with delayed motor development, intellectual disability, and dystonia. Magnetic resonance imaging revealed hypomyelination and progressive cerebellar atrophy without atrophy of the basal ganglia. Whole-exome sequencing revealed a de novo heterozygous variant, c.1088T > C, p.(Met363Thr), in TUBB4A. The present case further supports the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants.