Genotype-phenotype correlation in vanishing white matter disease
H D W van der Lei1, C G M van Berkel, W N van Wieringen
1Department of Child Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Neurology
|October 27, 2010
Summary
The combination of mutations in the EIF2B5 gene influences the severity of vanishing white matter (VWM) disease. Females generally experience a milder disease course compared to males.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Vanishing white matter (VWM) is a severe autosomal recessive leukoencephalopathy.
- VWM results from mutations in eukaryotic initiation factor 2B (eIF2B) genes, crucial for protein translation.
- Significant variability exists in VWM onset, severity, and progression, with genotype-phenotype correlations unclear.
Purpose of the Study:
- To investigate the influence of specific EIF2B5 gene mutations on the clinical phenotype of VWM.
- To determine the impact of mutation combinations and gender on disease severity and progression.
Main Methods:
- Cross-sectional observational study of 184 VWM patients with defined EIF2B5 mutations.
- Analysis included patients with homozygous or compound-heterozygous p.Arg113His and p.Thr91Ala mutations.
- Clinical characteristics evaluated: gender, age at onset, motor milestones, and survival.
Main Results:
- Homozygous p.Arg113His mutations were associated with a milder VWM phenotype compared to compound heterozygous p.Arg113His or homozygous p.Thr91Ala.
- Patients with p.Arg113His/p.Arg339any showed milder phenotypes than those with p.Thr91Ala/p.Arg339any.
- Females consistently exhibited a milder disease course than males.
Conclusions:
- The specific combination of mutations in the EIF2B5 gene significantly shapes the clinical presentation of VWM.
- Gender is a notable factor, with females generally experiencing a less severe disease course than males.
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