{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T06:20:34Z","timestamp":1758349234242,"version":"3.44.0"},"reference-count":8,"publisher":"BMJ","issue":"9","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,9,2]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a disorder with an autosomal recessive mode of inheritance. It is caused by mutations of the <jats:italic>DARS2<\/jats:italic> gene that encodes aspartyl-transfer RNA (tRNA) synthetase enzymes responsible for the accurate charging of aspartate-specific tRNA with aspartate. Clinical features include seizures, cognitive impairment, cerebellar signs, upper motor neuron type of weakness, peripheral neuropathy, muscle weakness, cramps and deformities. Exclusive involvement of the peripheral nervous system has not been reported so far. We describe a case in which the patient presented with peripheral neuropathy mimicking hereditary motor and sensory neuropathy type 1, and genetic analysis revealed a <jats:italic>DARS2<\/jats:italic> mutation. This case highlights the potential phenotypic variability that can be associated with a <jats:italic>DARS2<\/jats:italic> mutation and the importance of comprehensive genetic testing in unexplained neuropathies, while acknowledging the limitations, as it is a variant of uncertain significance. More research is necessary to establish definite causation.<\/jats:p>","DOI":"10.1136\/bcr-2025-264880","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:35:28Z","timestamp":1758260128000},"page":"e264880","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Isolated peripheral neuropathy in a young adult: the role of comprehensive genetic testing"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0991-9563","authenticated-orcid":false,"given":"Deepa","family":"Avadhani","sequence":"first","affiliation":[{"name":"Department of Neurology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-637X","authenticated-orcid":false,"given":"Rithvik","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshmi Narasimhan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandeesh","family":"B N","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philo","family":"Hazeena","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sundar","family":"S","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"2025091822351590000_18.9.e264880.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.9.081307.164204"},{"key":"2025091822351590000_18.9.e264880.2","first-page":"4","article-title":"Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation: Two Siblings with A Novel Mutation in The DARS2 Gene. (P3.4-044)","volume":"92","author":"Yelam","year":"2019","journal-title":"Neurology (ECronicon)"},{"key":"2025091822351590000_18.9.e264880.3","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1002\/mdc3.13281","article-title":"Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation: A Novel DARS2 Mutation and Intra-Familial Heterogeneity","volume":"8","author":"Li","year":"2021","journal-title":"Mov Disord Clin Pract"},{"key":"2025091822351590000_18.9.e264880.4","doi-asserted-by":"crossref","first-page":"13042","DOI":"10.1038\/s41598-023-40107-7","article-title":"Mutations in DARS2 result in global dysregulation of mRNA metabolism and splicing","volume":"13","author":"Guang","year":"2023","journal-title":"Sci Rep"},{"key":"2025091822351590000_18.9.e264880.5","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1212\/WNL.0b013e31828cf846","article-title":"Teaching neuroimages: MRI guides genetics; leukoencephalopathy with brainstem and spinal cord involvement (LBSL)","volume":"80","author":"Schicks","year":"2013","journal-title":"Neurology"},{"key":"2025091822351590000_18.9.e264880.6","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9292-y"},{"key":"2025091822351590000_18.9.e264880.7","doi-asserted-by":"crossref","DOI":"10.3390\/genes15050615","article-title":"Identification of a Novel Indel Variant in the DARS2 Gene in Russian Patients with Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation","volume":"15","author":"Bostanova","year":"2024","journal-title":"Genes (Basel)"},{"key":"2025091822351590000_18.9.e264880.8","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.mcp.2015.06.005","article-title":"Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene","volume":"29","author":"K\u00f6hler","year":"2015","journal-title":"Mol Cell Probes"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2025-264880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:35:30Z","timestamp":1758260130000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2025-264880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":8,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,18]]},"published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1136\/bcr-2025-264880"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2025-264880","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,9]]}}}