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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'
Kirsten Svenstrup1, Geneviève Giraud, Odile Boespflug-Tanguy
1Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark. ksvenstrup@sund.ku.dk
Journal of Neurology, Neurosurgery, and Psychiatry
|December 4, 2009
Summary
The rumpshaker mutation causes a mild form of hereditary spastic paraplegia (HSP) with central demyelination but normal cognition. Female carriers showed no definite symptoms, suggesting a dysmyelinating disorder.
Area of Science:
- Neurogenetics
- Neurodegenerative Diseases
- Myelin Biology
Background:
- Hereditary spastic paraplegia (HSP) encompasses diverse neurodegenerative disorders causing progressive lower limb spasticity and weakness.
- Mutations in PLP1 gene lead to SPG2/PMD, affecting myelin sheath maintenance.
- The rumpshaker mouse model aids in studying SPG2/PMD.
Observation:
- Characterized the phenotype of patients with the 'rumpshaker mutation' in a family with HSP.
- Patients exhibited infantile nystagmus and early-onset HSP with normal cognition.
- Female carriers reported urinary urgency; MRI revealed non-specific white matter abnormalities.
Findings:
- Patients displayed severe central demyelination without peripheral involvement or axonal degeneration.
- MRS showed increased white matter myo-inositol; decreased N-acetylaspartate was noted in the oldest patient.
- (18)F-FDG-PET scans were normal, indicating preserved metabolic activity.
Implications:
- The 'rumpshaker mutation' presents the mildest phenotype within PLP1-related disorders.
- This suggests an underlying dysmyelinating disorder with secondary central axonal degeneration.
- The study found no definitive symptoms in female carriers, highlighting potential sex-specific disease expression or milder impact.
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