ArticleActa neuropathologica communications2019
An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.Orphanet journal of rare diseases · 2023Pooled it
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Advances in Research onGenes · 2026Review
- Clinical Diagnosis and Differential Diagnosis Between CSF1R- and AARS2-Related Leukoencephalopathy.Journal of molecular neuroscience : MN · 2025Article
- AARS and CACNA1A mutations: diagnostic insights into a case report of uncommon epileptic encephalopathy phenotypes in two siblings.Frontiers in neurology · 2024Article
- Clinical presentation and diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: a literature analysis of case studies.Frontiers in neurology · 2024Article
- Adult-Onset Genetic Leukoencephalopathies With Movement Disorders.Journal of movement disorders · 2023Article
- An AARS1 variant identified to cause adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia.Translational neurodegeneration · 2023Article
- Report of A Family with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Without Mutations inMovement disorders clinical practice · 2023Article
- Dominant aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Novel mitochondrial alanyl-tRNA synthetase 2 (AARS2) heterozygous mutations in a Chinese patient with adult-onset leukoencephalopathy.BMC neurology · 2022Article
- The Primary Microglial Leukodystrophies: A Review.International journal of molecular sciences · 2022Review
- Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes.Acta neurologica Scandinavica · 2022Observational
- Aminoacyl-tRNA synthetases in human health and disease.Frontiers in physiology · 2022Review
- Expanded phenotype of AARS1-related white matter disease.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Clinical and genetic characterization of adult-onset leukoencephalopathy caused by CSF1R mutations.Annals of clinical and translational neurology · 2021Article
- Case report: 'AARS2 leukodystrophy'.Molecular genetics and metabolism reports · 2021Article
- Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development.Frontiers in neurology · 2021Review
- Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy.Acta neuropathologica communications · 2020Review
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described in a large family with a dominant inheritance pattern. The initial stage of the disease is dominated by frontal lobe symptoms that develop into a rapidly advancing encephalopathy with pyramidal, deep sensory, extrapyramidal and optic tract symptoms. Median survival is less than 10 years. Recently, pathogenic mutations in CSF1R were reported in a clinically and histologically similar leukoencephalopathy segregating in several families. Still, the cause of HDLS-S remained elusive since its initial description in 1984, with no CSF1R mutations identified in the family. Here we update the original findings associated with HDLS-S after a systematic and recent assessment of several family members. We also report the results from exome sequencing analyses indicating the p.Cys152Phe variant in the alanyl tRNA synthetase (AARS) gene as the probable cause of this disease. The variant affects an amino acid located in the aminoacylation domain of the protein and does not cause differences in splicing or expression in the brain. Brain pathology in one case after 10 years of disease duration showed the end stage of the disease to be characterized by widespread liquefaction of the white matter leaving only some macrophages and glial cells behind the centrifugally progressing front. These results point to AARS as a candidate gene for rapidly progressing adult-onset CSF1R-negative leukoencephalopathies.
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