[P2-182] Eleven novel mutations in Chinese patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and A Long-term Follow-up Research
Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurodegenerative disease characterized by macrocephaly, motor development delay and abnormal white matter signals with subcortical cysts, caused by MLC1 or GlialCAM mutations. 30 patients were enrolled in this study. Macrocephaly and classic MRI features were found in 30(100%), motor development delay and mental retardation were detected in 24(80%) and 6(20%), respectively. 30(100%) patients were clinically diagnosed with MLC, with 25(83.3%) classic phenotype, 4(13.3%) improving phenotype, and 1(3.3%) loss to follow up not classified. 29(96.7%) were genetically diagnosed, with 23 in MLC1 and 6 in GlialCAM, identifying 8 and 3 novel mutations in MLC1 and GlialCAM, respectively. 23(76.7%) were type MLC1, 1(3.3%) type MLC2A and 5(16.7%) type MLC2B, and 1(3.3%) not genetically diagnosed was unclear. Exon4-exon9 deletion and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 led to exon8 skip. c.772-1G>C in MLC1 might be a founder or a hot-spot mutation in Chinese. Prenatal diagnosis was conducted for 2 families and no same mutations in both sites were detected in the fetuses. 27 patients were enrolled in the follow-up study. Head circumference was beyond the 95th percentile, with a median of 57cm in those older than 5 years old. Motor development was progressing at the early stage but delayed later, and deteriorated between 2.5 to 11 years old. Cranial MRI got recovered in a patient with improving phenotype. Cognitive ability was relatively spared and deterioration occurred in 2 patients. Seizures, unconsciousness and transient motor retrogress were found more after head trauma than after fever. This was a clinical and genetic analysis and a follow-up study with largest sample of Chinese MLC patients, identifying 11 novel mutations, expanding the mutation spectrum and discovering clinical features of Chinese MLC patients.