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Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL
Leigh syndrome (LS) is most frequently characterized by the presence of focal, bilateral, and symmetric brain lesions Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare condition, characterized by progressive pyramidal, cerebellar, and dorsal column...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697158/ https://www.ncbi.nlm.nih.gov/pubmed/33182419 http://dx.doi.org/10.3390/genes11111325 |
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author | Borna, Nurun Nahar Kishita, Yoshihito Sakai, Norio Hamada, Yusuke Kamagata, Koji Kohda, Masakazu Ohtake, Akira Murayama, Kei Okazaki, Yasushi |
author_facet | Borna, Nurun Nahar Kishita, Yoshihito Sakai, Norio Hamada, Yusuke Kamagata, Koji Kohda, Masakazu Ohtake, Akira Murayama, Kei Okazaki, Yasushi |
author_sort | Borna, Nurun Nahar |
collection | PubMed |
description | Leigh syndrome (LS) is most frequently characterized by the presence of focal, bilateral, and symmetric brain lesions Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare condition, characterized by progressive pyramidal, cerebellar, and dorsal column dysfunction. We describe a case with infantile-onset neurodegeneration, psychomotor retardation, irritability, hypotonia, and nystagmus. Brain MRI demonstrated signal abnormalities in the deep cerebral white matter, corticospinal and dorsal column tracts, and pyramids, which resemble the MRI pattern of a severe form of LBSL, and involvement of basal ganglia and thalamus that resemble the radiological features of LS. We identified biallelic loss-of-function mutations, one novel (c.756delC, p.Thr253Glnfs*44) and another reported (c.1156C > T, p.Arg386Cys), in NDUFV1 (NADH:Ubiquinone Oxidoreductase Core Subunit V1) by exome sequencing. Biochemical and functional analyses revealed lactic acidosis, complex I (CI) assembly and enzyme deficiency, and a loss of NDUFV1 protein. Complementation assays restored the NDUFV1 protein, CI assembly, and CI enzyme levels. The clinical and radiological features of this case are compatible with the phenotype of LS and LBSL associated with NDUFV1 mutations. |
format | Online Article Text |
id | pubmed-7697158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76971582020-11-29 Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL Borna, Nurun Nahar Kishita, Yoshihito Sakai, Norio Hamada, Yusuke Kamagata, Koji Kohda, Masakazu Ohtake, Akira Murayama, Kei Okazaki, Yasushi Genes (Basel) Article Leigh syndrome (LS) is most frequently characterized by the presence of focal, bilateral, and symmetric brain lesions Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare condition, characterized by progressive pyramidal, cerebellar, and dorsal column dysfunction. We describe a case with infantile-onset neurodegeneration, psychomotor retardation, irritability, hypotonia, and nystagmus. Brain MRI demonstrated signal abnormalities in the deep cerebral white matter, corticospinal and dorsal column tracts, and pyramids, which resemble the MRI pattern of a severe form of LBSL, and involvement of basal ganglia and thalamus that resemble the radiological features of LS. We identified biallelic loss-of-function mutations, one novel (c.756delC, p.Thr253Glnfs*44) and another reported (c.1156C > T, p.Arg386Cys), in NDUFV1 (NADH:Ubiquinone Oxidoreductase Core Subunit V1) by exome sequencing. Biochemical and functional analyses revealed lactic acidosis, complex I (CI) assembly and enzyme deficiency, and a loss of NDUFV1 protein. Complementation assays restored the NDUFV1 protein, CI assembly, and CI enzyme levels. The clinical and radiological features of this case are compatible with the phenotype of LS and LBSL associated with NDUFV1 mutations. MDPI 2020-11-09 /pmc/articles/PMC7697158/ /pubmed/33182419 http://dx.doi.org/10.3390/genes11111325 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Borna, Nurun Nahar Kishita, Yoshihito Sakai, Norio Hamada, Yusuke Kamagata, Koji Kohda, Masakazu Ohtake, Akira Murayama, Kei Okazaki, Yasushi Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title | Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title_full | Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title_fullStr | Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title_full_unstemmed | Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title_short | Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL |
title_sort | leigh syndrome due to ndufv1 mutations initially presenting as lbsl |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697158/ https://www.ncbi.nlm.nih.gov/pubmed/33182419 http://dx.doi.org/10.3390/genes11111325 |
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