Language
English
Publication Date
10-1-2024
Journal
Neurology Genetics
DOI
10.1212/NXG.0000000000200187
PMID
39280886
PMCID
PMC11398975
PubMedCentral® Posted Date
9-13-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Objectives: To highlight the worldwide presence of CSF1R-related disorder (CSF1R-RD), discuss its penetrance, and provide the first haplotype analysis.
Methods: Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct families with CSF1R p.Ile794Thr variant were examined.
Results: Nineteen new patients were included, at a mean age of 38.7 years (ranging from 11 to 74 years), from 14 families from the Americas, Asia, Australia, and Europe, including the first from Mexico, North Macedonia, and Ukraine. Fifteen CSF1R variants were found, including 8 novel. Three patients were compound heterozygotes with disease onset at 1, 4, and 22 years. Patients with heterozygous CSF1R variants developed symptoms at a mean of 39.0 years (range 8-71 years). Four patients died at a mean of 3.3 years from onset (range 2-5 years). Negative family history was noted in 7 patients. In haplotype analysis, 2 families exhibited shared haplotype encompassing ∼6-Mb region downstream of the CSF1R while the third family displayed a different haplotype.
Discussion: CSF1R-RD has a global prevalence. The reasons for negative family history include de novo variants (as shown by the haplotype analysis), mosaicism, and incomplete penetrance, which are possibly modulated by environmental and genetic factors.
Published Open-Access
yes
Recommended Citation
Dulski, Jaroslaw; Baker, Matthew; Banks, Samantha A; et al., "Global Presence and Penetrance of" (2024). Faculty, Staff and Students Publications. 7692.
https://digitalcommons.library.tmc.edu/baylor_docs/7692