A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study
Harumi Saijo1, Harumi Nakayama, Takanori Ezoe
1Tokyo Metropolitan Higashiyamato Medical Center for the Severely Disabled, 3-44-10 Sakuragaoka, Higashiyamato, Tokyo 207-0022, Japan.
Abstract:
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor function with ataxia, spasticity and mental decline. It has been revealed that the mutations in the gene, KIAA0027, were responsible for MLC and the gene was renamed subsequently 'MLC1'. A 41-year-old Japanese male with MLC, in whom a homozygous missense mutation, TCG to TTG at codon 93 resulting in S93L, was detected in the MLC1 gene, was described. MRI revealed marked cerebral atrophy and enlargement of the ventricular system. The subject's motor function had severely deteriorated, while his cognitive function had maintained at the level of a 2-year-old for the past 10 years. The mutation in the MLC1 gene of the patient is considered to be a common mutation responsible for MLC in Japanese patients because the same mutation had been detected in two other Japanese patients with MLC.
Insights
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a genetic disorder. A common Japanese MLC1 gene mutation, S93L, was identified in a patient, suggesting its prevalence in the population.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive neurological disorder.
- Key features include macrocephaly, motor function decline, ataxia, spasticity, and cognitive impairment.
- The MLC1 gene (formerly KIAA0027) is implicated in the pathogenesis of MLC.
Observation:
- A case study of a 41-year-old Japanese male with MLC.
- The patient presented with macrocephaly, severe motor deterioration, and preserved cognitive function (equivalent to a 2-year-old).
- MRI revealed significant cerebral atrophy and ventricular enlargement.
Findings:
- A homozygous missense mutation (TCG to TTG at codon 93, resulting in S93L) was identified in the MLC1 gene.
- This specific S93L mutation in MLC1 is considered a common cause of MLC in Japanese patients.
- The same mutation was previously found in two other Japanese MLC patients.
Implications:
- This finding highlights the S93L mutation as a significant genetic factor in Japanese populations with MLC.
- Understanding the prevalence of specific mutations aids in genetic diagnosis and counseling for MLC.
- Further research into MLC1 mutations can inform therapeutic strategies for leukodystrophies.
