Central nervous system abnormalities in patients with PMP22 gene mutations: a prospective study
Jean-Baptiste Chanson1, Andoni Echaniz-Laguna, Frédéric Blanc
1Department de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, 1 avenue Molière, Strasbourg 67000, France. jean-baptiste.chanson@chru-strasbourg.fr
Journal of Neurology, Neurosurgery, and Psychiatry
|December 18, 2012
Summary
Peripheral myelin protein-22 (PMP22) gene mutations cause central nervous system (CNS) abnormalities in hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth 1A (CMT1A) disease. Patients exhibit white matter volume reduction and cognitive impairment, indicating PMP22
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Peripheral myelin protein-22 (PMP22) gene mutations are primary causes of inherited peripheral nervous system (PNS) disorders, including HNPP and CMT1A.
- While PMP22 is primarily in the PNS, its presence in the CNS suggests potential central effects.
Purpose of the Study:
- To investigate the presence and nature of central nervous system (CNS) abnormalities in patients with PMP22 gene mutations.
- To determine if PMP22 mutations correlate with structural and metabolic changes in the brain.
Main Methods:
- Brain MRI, including volumetric analysis of grey and white matter (GM and WM), and fractional anisotropy (FA) for WM architecture.
- Neuropsychological assessments and brain spectroscopy to evaluate metabolic changes (e.g., creatine levels).
- Post-mortem CNS examination in a case of PMP22 gene duplication.
Main Results:
- Reduced white matter (WM) volume observed in 70% of patients.
- Cognitive impairment detected in 70% of patients, with altered WM creatine levels in 28%.
- Significant alterations in WM fractional anisotropy (FA) and diffuse hypomyelination noted in post-mortem analysis.
Conclusions:
- Altered PMP22 gene expression is linked to significant CNS abnormalities in HNPP and CMT1A patients.
- Cerebral white matter abnormalities and cognitive deficits are key manifestations of PMP22-related disorders.
- Findings highlight the impact of PMP22 on both peripheral and central nervous systems.
