Objective: To report the clinical and pathological features of CSF1R-RD associated with the c.2330G>A, p.R777Q variant, and to report a new family carrying this variant.

Background: Colony-stimulating factor-1 receptor (CSF1R)-related disorder (CSF1R-RD) is a rapidly progressive neurodegenerative disease with a median age of onset of 43 years. Most affected individuals develop rapidly progressive dementia and motor symptoms and eventually become bedridden; median disease duration is 6.8 years. More than 200 CSF1R pathogenic variants have been identified, but no genotype-phenotype correlation has been established. The c.2330G>A, p.R777Q variant has been reported previously as causative for CSF1R-RD; in silico analysis supports that this missense variant has a deleterious effect on protein structure/function

Method: We performed a literature search for CSF1R-RD associated with the c.2330G>A, p.R777Q variant and compared the collected data with data available from our new family.

Results: We identify 13 individuals from 8 families including ours affected by CSF1R-RD associated with the c.2330G>A, p.R777Q variant from Asia, Europe, and North America. The mean age of onset was 40.8±13.5 years (ranging from 22 to 63 years), and the mean survival was only 3.0±2.2 years. Brain autopsy of our index patient showed diffuse leukoencephalopathy with spheroids and pigmented glia, most severe in the frontal and parietal lobes; white matter was spared in the temporal and occipital lobes.

Conclusion: CSF1R-RD associated with the c.2330G>A, p.R777Q variant has a typical clinical and radiologic presentation of CSF1R-RD. Although the mean age of onset was close to that reported in the literature for all mutations, but it had a very wide range. In addition, the patients carrying this variant had a short survival, shorter than mean survival time for all mutations. Pathological abnormalities were like those observed on autopsies of other pathogenic variants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-pathological-features-of-csf1r-related-disorder-associated-with-the-c-2330ga-p-r777q-pathogenic-variant/