Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Pediatr Neurol. 2011 Jun;44(6):450-8. doi: 10.1016/j.pediatrneurol.2011.01.003.
Mutations in the MLC1 gene cause megalencephalic leukoencephalopathy with subcortical cysts. We sought to identify mutations in the MLC1 gene, to evaluate the genotype-phenotype correlation, and to develop a strategy for diagnosing Indian patients with megalencephalic leukoencephalopathy. Forty patients were enrolled. We developed a rapid restriction fragment length polymorphism method to screen a common mutation, c.135_136insC. Rare and novel mutations were screened by conformation-sensitive gel electrophoresis, followed by sequencing. Three previously reported and two novel mutations were identified in 37 patients. The presence of the c.135_136insC mutation in 29 patients of the Agarwal community suggests a founder effect. The mutation c.959C>A was evident in four patients, and appears to be the second commonest mutation. Genotype could not predict phenotype. We recommend screening for the commonest mutation (c.135_136insC), followed by the next commonest mutation (c.959C>A), and then other rare mutations, using conformation-sensitive gel electrophoresis analysis or direct sequencing.
MLC1 基因突变导致巨脑性脑白质病伴皮质下囊肿。我们试图鉴定 MLC1 基因突变，评估基因型-表型相关性，并为诊断印度巨脑性脑白质病患者制定策略。共纳入 40 例患者。我们开发了一种快速的限制片段长度多态性方法来筛查常见的突变 c.135_136insC。通过构象敏感凝胶电泳筛选罕见和新的突变，然后进行测序。在 37 例患者中发现了 3 个先前报道的和 2 个新的突变。Agarwal 社区 29 例患者中存在 c.135_136insC 突变提示存在一个奠基者效应。在 4 例患者中发现了突变 c.959C>A，其似乎是第二常见的突变。基因型不能预测表型。我们建议使用构象敏感凝胶电泳分析或直接测序，首先筛查最常见的突变（c.135_136insC），然后是下一个常见的突变（c.959C>A），然后是其他罕见的突变。
