[P2-183] MLC1 mutations in Japanese patients with megalencephalic leukoencephalopathy with subcortical cysts
[Introduction] Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive neurological disorder manifesting early onset macrocephaly and delayed-onset neurological deterioration. Characteristic radiological findings revealed by brain magnetic resonance imaging are the most important factors for obtaining a clinical diagnosis. The causative gene MLC1 was first identified in 2001 and maps to chromosome band 22q13.33. MLC1 mutations have been observed in 75% of patients with MLC. We report the results of an ongoing study to obtain a genetic diagnosis of MLC1. [Results] The most common mutation in our study was p.S93L; this mutation was observed in 12alleles (75%). The second most common mutation, p.A275D, was observed in two alleles (12.5%). A novel single-nucleotide deletion, c.578delG (p.V194fs) was identified in one allele. Two infant patients were diagnosed with MLC as a result of examination for macrocephaly; no neurological findings were observed in either of these two patients at the time of genetic diagnosis. The severities of patients with the p.S93L homozygous mutation was variable, ranging from mild cognitive to bedridden. In three patients, provoked events was observed after head trauma and high fever. [Conclusions] As the clinical severities of patients with MLC were variable even among those sharing identical genotypes, this condition may be modified by environmental factors, modifier genes or epigenetic factors.