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Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report

BACKGROUND: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion s...

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Autores principales: Kume, Kodai, Morino, Hiroyuki, Miyamoto, Ryosuke, Matsuda, Yukiko, Ohsawa, Ryosuke, Kanaya, Yuhei, Tada, Yui, Kurashige, Takashi, Kawakami, Hideshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110654/
https://www.ncbi.nlm.nih.gov/pubmed/32234020
http://dx.doi.org/10.1186/s12881-020-01002-4
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author Kume, Kodai
Morino, Hiroyuki
Miyamoto, Ryosuke
Matsuda, Yukiko
Ohsawa, Ryosuke
Kanaya, Yuhei
Tada, Yui
Kurashige, Takashi
Kawakami, Hideshi
author_facet Kume, Kodai
Morino, Hiroyuki
Miyamoto, Ryosuke
Matsuda, Yukiko
Ohsawa, Ryosuke
Kanaya, Yuhei
Tada, Yui
Kurashige, Takashi
Kawakami, Hideshi
author_sort Kume, Kodai
collection PubMed
description BACKGROUND: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perrault syndrome 5. Perrault syndrome is characterized by sensorineural hearing loss in both males and females and gonadal dysfunction in females. Patients with Perrault syndrome may present early-onset cerebellar ataxia, whereas middle-age-onset cerebellar ataxia caused by TWNK variants is rare. CASE PRESENTATION: A Japanese female born to consanguineous parents presented hearing loss at age 48, a staggering gait at age 53, and numbness in her distal extremities at age 57. Neurological examination revealed sensorineural hearing loss, cerebellar ataxia, decreased deep tendon reflexes, and sensory disturbance in the distal extremities. Laboratory tests showed no abnormal findings other than a moderate elevation of pyruvate concentration levels. Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM_021830: c.1358G>A, p.R453Q). CONCLUSIONS: TWNK variants could cause middle-age-onset cerebellar ataxia. Screening for TWNK variants should be considered in cases of cerebellar ataxia associated with deafness and/or peripheral neuropathy, even if the onset is not early.
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spelling pubmed-71106542020-04-07 Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report Kume, Kodai Morino, Hiroyuki Miyamoto, Ryosuke Matsuda, Yukiko Ohsawa, Ryosuke Kanaya, Yuhei Tada, Yui Kurashige, Takashi Kawakami, Hideshi BMC Med Genet Case Report BACKGROUND: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perrault syndrome 5. Perrault syndrome is characterized by sensorineural hearing loss in both males and females and gonadal dysfunction in females. Patients with Perrault syndrome may present early-onset cerebellar ataxia, whereas middle-age-onset cerebellar ataxia caused by TWNK variants is rare. CASE PRESENTATION: A Japanese female born to consanguineous parents presented hearing loss at age 48, a staggering gait at age 53, and numbness in her distal extremities at age 57. Neurological examination revealed sensorineural hearing loss, cerebellar ataxia, decreased deep tendon reflexes, and sensory disturbance in the distal extremities. Laboratory tests showed no abnormal findings other than a moderate elevation of pyruvate concentration levels. Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM_021830: c.1358G>A, p.R453Q). CONCLUSIONS: TWNK variants could cause middle-age-onset cerebellar ataxia. Screening for TWNK variants should be considered in cases of cerebellar ataxia associated with deafness and/or peripheral neuropathy, even if the onset is not early. BioMed Central 2020-03-31 /pmc/articles/PMC7110654/ /pubmed/32234020 http://dx.doi.org/10.1186/s12881-020-01002-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Kume, Kodai
Morino, Hiroyuki
Miyamoto, Ryosuke
Matsuda, Yukiko
Ohsawa, Ryosuke
Kanaya, Yuhei
Tada, Yui
Kurashige, Takashi
Kawakami, Hideshi
Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title_full Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title_fullStr Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title_full_unstemmed Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title_short Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report
title_sort middle-age-onset cerebellar ataxia caused by a homozygous twnk variant: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110654/
https://www.ncbi.nlm.nih.gov/pubmed/32234020
http://dx.doi.org/10.1186/s12881-020-01002-4
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