Journal article
The neuropathologic findings in a case of progressive cavitating leukoencephalopathy due to NDUFV1 pathogenic variants
Acta neuropathologica communications, Vol.10(1), 142
09/26/2022
DOI: 10.1186/s40478-022-01445-1
PMCID: PMC9511743
PMID: 36163075
Abstract
Pathogenic variants in the NDUFV1 gene, which codes for complex I of the mitochondrial respiratory chain, have been associated with a variety of clinical phenotypes, including a progressive cavitating leukoencephalopathy. The neuropathology of NDUFV1-associated leukoencephalopathy is not well-described. We present a report of a 24-year-old female with two pathogenic variants in the NDUFV1 gene, together with antemortem skeletal muscle biopsy and postmortem neuropathologic examination. Autopsy neuropathology showed a cavitating leukoencephalopathy with extensive white matter involvement, regions of active demyelination, and sparing of the subcortical U-fibers. Muscle biopsy showed subtle but distinct histologic abnormalities by light microscopy, and ultrastructural analysis demonstrated mitochondrial abnormalities including abnormal subsarcolemmal mitochondrial accumulation, electron-dense inclusions, and enlarged mitochondria with abnormal cristae. Our report is the first comprehensive description of the neuropathology in a patient with compound heterozygous variants in the NDUFV1 gene and progressive cavitating leukoencephalopathy. This case is evidence of pathogenicity of one NDUFV1 variant (c.565 T > C, p.S189P), which has not been previously described as pathogenic. These findings, in combination with the ultrastructural abnormalities in the mitochondria by electron microscopy, support the mitochondrial nature of the pathology. Together, this case highlights the link between mitochondrial abnormalities and demyelinating processes in the central nervous system (CNS).
Details
- Title: Subtitle
- The neuropathologic findings in a case of progressive cavitating leukoencephalopathy due to NDUFV1 pathogenic variants
- Creators
- Nicole Becker - University of IowaAditi Sharma - University of IowaMatthew Gosse - University of IowaBrooke Kubat - University of IowaKyle S Conway - University of Michigan–Ann Arbor
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica communications, Vol.10(1), 142
- DOI
- 10.1186/s40478-022-01445-1
- PMID
- 36163075
- PMCID
- PMC9511743
- ISSN
- 2051-5960
- eISSN
- 2051-5960
- Language
- English
- Date published
- 09/26/2022
- Academic Unit
- Pathology
- Record Identifier
- 9984640611302771
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