Category: Genetics (Non-PD)
Objective: The study aimed to assess the occurrence of CSF1R-related disorder (CSF1R-RD) and present the first haplotype analysis.
Background: Since the discovery of CSF1-R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids, CSF1R-RD has been distinctly characterized clinically, radiologically, and pathologically. It most commonly manifests with a frontotemporal dementia-like phenotype with motor symptoms, including pyramidal and extrapyramidal signs. As genetic testing becomes more widely available, the number of detected cases has increased significantly, but still little is known about their penetrance and other genotype-phenotype correlations.
Method: The study collected new cases of CSF1R-RD diagnosed at various centers around the world. Data collected included country of origin, ethnicity, sex, age, family history, clinical symptoms, age of symptom onset, and age of death. For three different families with the CSF1R p.Ile794Thr mutation, tandem repeat polymorphisms were investigated for haplotype analysis.
Results: A total of 19 individuals from 14 families with CSF1R-RD were identified from Asia (India), Australia, Europe (Belgium, Denmark, Hungary, Northern Macedonia, Ukraine), and the Americas (Brazil, Canada, Mexico, United States). The mean age was 38.7 years. Fifteen CSF1-R mutations were found, eight of which had not been previously reported. Three individuals were compound heterozygous for CSF1R mutations with onset of symptoms at ages 1, 4, and 22 years. In patients with heterozygous CSF1R mutations, the mean age of symptom onset was 39.0 years. It should be noted that in seven cases the patients had a negative family history (5 heterozygotes and 2 compound heterozygotes for CSF1R mutations). Two families shared haplotype in the D5S1469, D5S410, and D5S820 markers, encompassing a ~6Mb region downstream of the CSF1R p.Ile794Thr mutation.
Conclusion: CSF1R-RD occurs worldwide in various ethnic groups. Gene penetrance is incomplete, and the age of onset may vary. The possibility of de novo mutations and mosaicism should also be considered.
To cite this abstract in AMA style:
J. Dulski, M. Baker, S. Banks, M. Bayat, R. Bruffaerts, T. Chmiela, G. Cruz, C. Disserol, K. Fisher, N. Jainy, B. Kálmán, O. Kantarci, D. Maltsev, C. Middleton, G. Novotni, D. Plaseska-Karanfilska, S. Raskin, J. Souza, H. Teive, Z. Wszolek. Global presence and penetrance of CSF1R-Related disorder [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/global-presence-and-penetrance-of-csf1r-related-disorder/. Accessed June 15, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/global-presence-and-penetrance-of-csf1r-related-disorder/