Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes

Igal Rosenstein, Oluf Andersen, Daniel Victor, Elisabet Englund, Tobias Granberg, Carola Hedberg-Oldfors, Katarina Jood, Yusran Ady Fitrah, Takeshi Ikeuchi, Virginija Danylaité Karrenbauer

Research output: Contribution to journalArticlepeer-review

Abstract

Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare, genetic disease caused by heterozygous mutations in the CSF1R gene with rapidly progressive neurodegeneration, behavioral, cognitive, motor disturbances. Objective: To describe four cases of CSF1R-related leukoencephalopathy from three families with two different pathogenic mutations in the tyrosine kinase domain of CSF1R and to develop an integrated presentation of inter-individual diversity of clinical presentations. Methods: This is an observational study of a case series. Patients diagnosed with CSF1R encephalopathy were evaluated with standardized functional estimation scores and subject to analysis of cerebrospinal fluid biomarkers. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were evaluated. We performed a functional phosphorylation assay to confirm the dysfunction of mutated CSF1R protein. Results: Two heterozygous missense mutations in the CSF1R gene were identified, c.2344C>T; p.Arg777Trp and c.2329C>T; p.Arg782Cys. A phosphorylation assay in vitro showed markedly reduced autophosphorylation in cells expressing mutations. According to ACMG criteria, both mutations were pathogenic. A radiological investigation revealed typical white matter lesions in all cases. There was inter-individual diversity in the loss of cognitive, motor-neuronal, and extrapyramidal functions. Conclusions: Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.

Original languageEnglish
Pages (from-to)599-609
JournalActa Neurologica Scandinavica
Volume145
Issue number5
Early online date2022
DOIs
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Medical Genetics

Free keywords

  • adult-onset leukoencephalopathy with spheroids and pigmented glia
  • biomarkers
  • colony stimulating factor 1 receptor
  • CSF1R gene
  • neurodegeneration
  • primary microgliopathy

Fingerprint

Dive into the research topics of 'Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes'. Together they form a unique fingerprint.

Cite this