Ataxia - adult onset

Gene: CSF1R

Green List (high evidence)

Most pathogenic variants in this gene were reported for Hereditary diffuse leukoencephalopathy with spheroids (HDLS): AD, haploinsuff, missense & PTCs, almost all the dominant CSF1R mutations reported in HDLS are within the intracellular kinase domain.

AR mechanism - PTCs & missense reported, LoF shown by functional studies.
AD mechanism - Clustering of pathogenic missense within the kinase domain and this protein's ability to homodimerise is strongly suggestive of DN. While some papers have shown coexpression with wildtype to potentially have no effect on protein function, other strongly believe the LOF mechanism isnt not valid due to asymptomatic carriers

Created: 18 Sep 2020, 1:33 a.m. | Last Modified: 18 Sep 2020, 1:33 a.m.

Panel Version: 0.4486

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476); Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820)

Publications

• PMID: 31330095
• 24336230

Mode of pathogenicity
Other

Green List (high evidence)

At least 6 reported cases where ataxia is a feature of the condition.
Sources: Literature

Created: 4 Feb 2020, 10:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Leukoencephalopathy, diffuse hereditary, with spheroids MIM#221820; ataxia

Publications

• 24198292
• 25563800
• 25935893