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. 2023 Dec;21(6):475-478.
doi: 10.1055/s-0043-1771352. Epub 2023 Jul 28.

DNM1L variant presenting as adolescent-onset sensory neuronopathy, spasticity, dystonia, and ataxia

Alexander S Wang  1   2 , Gabrielle Lemire  3   4 , Grace E VanNoy  3 , Christina Austin-Tse  3 , Anne O'Donnell-Luria  3   4 , Camilla Kilbane  1   2
Affiliations

DNM1L variant presenting as adolescent-onset sensory neuronopathy, spasticity, dystonia, and ataxia

Alexander S Wang et al. J Pediatr Neurol. 2023 Dec.

Abstract

DMN1L encodes for dynamin-like protein 1 (DLP1) which plays a key role in perixosomal and mitochondrial fission. Individuals with heterozygous variants in DNM1L present with a wide range of neurologic symptoms, including encephalopathy, epilepsy, and motor deficits. Here we report on a woman presenting with adolescence onset of sensory neuronopathy, spasticity, dystonia, and ataxia. Trio genome sequencing identified a heterozygous variant in DNM1L (NM_012062.3 c.121G>A/p.Val41Met) which was thought to be pathogenic. This case describes the latest known symptomatic onset of DMN1L-related disease described in literature. We highlight our approach to a challenging diagnostic workup and interpretation of a specific variant that has not been previously reported. Furthermore, the case highlights the diagnostic importance of utilizing genomic sequencing and research studies for patients with rare disease.

Keywords: DLP1; DNM1L; ataxia; dystonia; mitochondrial; neuropathy; sensory neuronopathy; spasticity.

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Conflict of interest statement

Conflicts of interest: The authors have no relevant conflicts of interest to disclose.

Figures

Figure 1
Figure 1
EMG and nerve conduction study at age 28 demonstrating non-length dependent pure sensory neuropathy, consistent with sensory neuronopathy.
See this image and copyright information in PMC

References

    1. Chen H, Chan DC. Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases. Hum Mol Genet. Oct 15 2009;18(R2):R169–76. doi:10.1093/hmg/ddp326 - DOI - PMC - PubMed
    1. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. Oct 19 2006;443(7113):787–95. doi:10.1038/nature05292 - DOI - PubMed
    1. Meyer JN, Leuthner TC, Luz AL. Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology. Nov 1 2017;391:42–53. doi:10.1016/j.tox.2017.07.019 - DOI - PMC - PubMed
    1. Kraus F, Roy K, Pucadyil TJ, Ryan MT. Function and regulation of the divisome for mitochondrial fission. Nature. Feb 2021;590(7844):57–66. doi:10.1038/s41586-021-03214-x - DOI - PubMed
    1. Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. Aug 31 2012;337(6098):1062–5. doi:10.1126/science.1219855 - DOI - PMC - PubMed

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