A novel mutation in the CSF1R gene causes a variable leukoencephalopathy with spheroids
Roberta La Piana1, Alina Webber, Marie-Christine Guiot
1Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, 3801 University Street, Room 622, Montreal, QC, H3A 2B4, Canada, roberta.lapiana@mail.mcgill.ca.
Neurogenetics
|July 12, 2014
Summary
Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is linked to novel CSF1R mutations. This case shows significant intrafamilial variability and suggests HDLS may overlap with other leukoencephalopathies.
Area of Science:
- Neurogenetics
- Neurodegenerative Diseases
Background:
- Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a rare neurodegenerative disorder linked to mutations in the colony-stimulating factor 1 receptor gene (CSF1R).
- Understanding the phenotypic spectrum and genetic basis of HDLS is crucial for diagnosis and management.
Observation:
- A 44-year-old woman presented with neurological signs and cognitive decline, with suspected HDLS based on frontal leukoencephalopathy and neuroaxonal spheroids on brain biopsy.
- She carried a novel CSF1R exon 18 missense mutation (c.2350G>A; p.V784M), also identified in her mother who has bipolar disorder and white matter abnormalities.
Findings:
- This is the first report of HDLS caused by this specific novel CSF1R missense mutation.
- The findings suggest marked intrafamilial variability or incomplete penetrance associated with CSF1R mutations.
- A bone cyst observed in the patient supports a potential phenotypic overlap between HDLS and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.
Implications:
- This case expands the known spectrum of CSF1R mutations causing HDLS.
- It highlights the importance of considering genetic testing for CSF1R in patients with unexplained leukoencephalopathy and neuroaxonal spheroids.
- The potential overlap in phenotypes suggests a shared underlying pathophysiology or a spectrum of related disorders.
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