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Megalencephalicleukoencephalopathy with subcortical cysts (MLC) is an autosomal inheriteddisease resulting from MLC1 or GLIALCAM mutations. MLC can befurther classified to three types: MLC1, MLC2A, MLC2B due to different clinicalfindings and prognosis caused by different genotypes in different inheritedmanner. The analysis of clinical features, mutation screening and follow-upstudy were performed in twenty Chinese patients in this study. The clinicalcharacteristics of Chinese MLC patients were similar with reports abroadincluding early-onset macrocephaly, fast head growth rate, gross motordevelopmental delay and characteristic abnormalities on cranial MRI. TheChinese patients with MLC1- and GLIALCAM-related MLC were 80% and15%, respectively. Mutation spectrums were expended by the novel mutations of MLC1and GLIALCAM in these Chinese patients including 6 novel mutations of MLC1(c.803C>G (p.T268R); c.824C>A (p.A275T); c.858C>G(p.I286M);c.881C>T(p.P294L); c.596delCAgt(p.S199Cfs220X) and one splicing mutationc.895-1G>A in IVS11-1) and 2 novel mutations of GLIALCAM (c.203A>T(p.K68M);c.395C>A(p.T132N)). Mutation c.772-1G>C in IVS9-1 was supposed to be ahot spot mutation in present study or a founder mutation of Chinese MLCpatients. The disease progress from follow-up were analyzed systemically. Mostdemonstrated relative stable, while temporary deterioration induced by minorhead trauma was common. No evident genotype-phenotype correlations in MLC1patients, however the patient with homozygous c.772-1G>C mutation might be showeda severe phenotype. The results might provide the exact genetic counseling andfuture prenatal diagnosis for those MLC pedigrees and could be useful forunderstanding the natural history and the genotype-phenotype correlation ofthis disease.

megalencephalic leukoencephalopathy with subcortical cysts; MLC1; GLIALCAM; follow-up