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oai:hama-med.repo.nii.ac.jp:00003614 2023-08-02T05:23:29Z 1:11

POLR3A variants in striatal involvement without diffuse hypomyelination Hiraide, Takuya Kubota, Kazuo Kono, Yu Watanabe, Seiji Matsubayashi, Tomoko Nakashima, Mitsuko Kaname, Tadashi Fukao, Toshiyuki Shimozawa, Nobuyuki Ogata, Tsutomu Saitsu, Hirotomo Copyright 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. POLR3A POLR3-related leukodystrophy 4H leukodystrophy striatal involvement whole-exome sequencing Background: Biallelic variants in POLR3A encoding the largest subunit of RNA polymerase III cause POLR3-related (or 4H) leukodystrophy characterized by neurologic dysfunction, abnormal dentition, endocrine abnormalities and ocular abnormality. Recently, whole-exome sequencing enabled the discovery of POLR3A variants in cases lacking diffuse hypomyelination, the principal MRI phenotype of POLR3-related leukodystrophy. Homozygous c.1771-6C>G variants in POLR3A were recently suggested to cause striatal and red nucleus involvement without white matter involvement. Case report: Here, we report three cases in two families with biallelic POLR3A variants. We identified two sets of compound heterozygous variants in POLR3A, c.1771-6C>G and c.791C>T, p.(Pro264Leu) for family 1 and c.1771-6C>G and c.2671C>T, p.(Arg891*) for family 2. Both families had the c.1771-6C>G variant, which led to aberrant mRNA splicing. Neuropsychiatric regression and severe intellectual disability were identified in three patients. Two cases showed dystonia and oligodontia. Notably, characteristic bilateral symmetric atrophy and abnormal signal of the striatum without diffuse white matter signal change were observed in brain MRI of all three individuals. Conclusions: Striatum abnormalities may be another distinctive MRI finding associated with POLR3A variants, especially in cases including c.1771-6C>G variants and our cases can expand the phenotypic spectrum of POLR3A-related disorders. Elsevier 2020-04 eng journal article AM http://hdl.handle.net/10271/00003746 https://hama-med.repo.nii.ac.jp/records/3614 31932101 10.1016/j.braindev.2019.12.012 0387-7604 1872-7131 Brain and Development 42 4 363 368 https://hama-med.repo.nii.ac.jp/record/3614/files/Brain Dev-42-363.pdf application/pdf 788.4 kB 2021-05-01