Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency
C T Gay1, L J Hardies, R A Rauch
1Department of Pediatrics, University of Texas Health Science Center at San Antonio, 78284, USA.
Abstract:
Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.
Insights
Magnetic resonance imaging (MRI) reveals incomplete brain myelination in 18q- syndrome. This is linked to the myelin basic protein (MBP) gene, suggesting haploinsufficiency contributes to the disorder.
Area of Science:
- Neuroimaging
- Genetics
- Developmental Biology
Background:
- 18q- syndrome is a genetic disorder associated with intellectual disability and developmental issues.
- Brain myelination is crucial for cognitive function and neurological development.
Purpose of the Study:
- To investigate brain myelination abnormalities in 18q- syndrome using MRI and MRI relaxometry.
- To correlate MRI findings with the status of the myelin basic protein (MBP) gene.
Main Methods:
- Acquisition of T1-weighted and dual spin-echo T2-weighted MRI scans.
- Creation of T1 and T2 parametric image maps for 20 patients with 18q- syndrome and 12 controls.
- Fluorescence in situ hybridization (FISH) for myelin basic protein (MBP) gene copy number analysis.
Main Results:
- All patients with 18q- syndrome exhibited abnormal white matter on MRI.
- Significantly prolonged white matter T1 and T2 relaxation times were observed in patients, indicating incomplete myelination.
- Patients with abnormal MRI and prolonged relaxation times were found to have a deletion in one copy of the MBP gene (haploinsufficiency).
Conclusions:
- Incomplete cerebral myelination in 18q- syndrome is associated with haploinsufficiency of the myelin basic protein (MBP) gene.
- MRI and genetic analysis provide insights into the neurobiological underpinnings of 18q- syndrome.
