Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T > G, p.Ile324Ser; c.344 T > C, p.Phe115Ser; and c.881 C > T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C > T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1 mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1 gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1 gene compared with other populations from the 1000-genome project.

MLC1的突变导致伴有皮质下囊肿 (MLC) 的巨脑性白质脑病，这是一种罕见的脑白质营养不良，其特征是大头畸形、癫痫、痉挛和缓慢的精神退化。世界许多地方都缺乏 MLC 的遗传学研究，尤其是在撒哈拉以南非洲地区。提取了来自 43 个苏丹家庭的 67 名脑白质营养不良患者的基因组 DNA。使用测试 139 种脑白质营养不良和白质脑病导致基因的 NGS 小组（NextSeq500 Illumina）筛选突变。五纯合MLC1在来自五个不同家庭的七名患者中发现了变异，其中包括来自苏丹同一地区的三个近亲家庭。三个变体是错义的（c.971 T > G，p.Ile324Ser；c.344 T > C，p.Phe115Ser；和 c.881 C > T，p.Pro294Leu），一个重复（c.831_838dupATATCTGT，p.Ser280Tyrfs *8) 和一个同义/剪接位点突变 (c.762 C > T, p.Ser254)。分离模式与常染色体隐性遗传一致。7 名受累患者的临床表现和脑部 MRI 均与 MLC1 的诊断一致。由于在我们的脑白质营养不良苏丹家族中发现了高频率的不同MLC1突变，我们分析了MLC1的编码序列与 1000 基因组计划相比，来自苏丹基因组计划的 124 个个体的基因。我们发现，与 1000 基因组计划的其他人群相比，苏丹的MLC1基因有害变异比例最高。