Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation
Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation
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DOI：
10.1212/01.wnl.0000115106.88813.5b
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发表时间：
2004-03-23
期刊：
影响因子：
9.9
通讯作者：
Naidu, S
中科院分区：
文献类型：
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作者：
Gorospe, JR;Singhal, BS;Naidu, S
工作背景：在印度的一个特定种族（Agarwals）中描述了一种独特的临床综合征，其特征为巨脑畸形、轻度至中度认知能力下降、缓慢进行性痉挛、共济失调、偶尔癫痫发作和广泛的白色物质变化伴颞叶囊肿（通过成像研究）。这种疾病与巨脑白质脑病伴皮质下囊肿（MLC）非常相似，MLC是一种新的特征性脑白质营养不良，其分子基础最近被证明是基因（KIAA 0027）突变，已更名为MLC 1。目的：通过对受影响的Agarwal患者进行的突变筛查研究，确定Agarwal患者中的这种疾病是否是由于MLC 1突变所致。研究方法：从这些印度脑白质营养不良患者的基因组DNA中筛选MLC 1基因的整个编码区（包括外显子-内含子边界）的突变。结果：筛选出33例临床和影像学表现符合MLC的患者。所有患者均来自印度北方，包括31名已知的Agarwal患者、1名非Agarwal患者和1名种族不详的收养患者。所有31名Agarwal患者在外显子2中的胞嘧啶纯合插入检测呈阳性。所收养的患者为A157 E纯合子。在非Agarwal患者中未发现编码区突变。结论：印度患者巨脑畸形和MRI变化显示广泛的白色物质变化与颞囊肿应提高怀疑MLC。Agarwal种族群体的成员患有这种疾病，表现为轻度进展过程，并在MLC 1基因中显示出常见的突变（320 insC），这表明了创始人效应。
Background: A distinct clinical syndrome characterized by megalencephaly, mild to moderate cognitive decline, slowly progressive spasticity, ataxia, occasional seizures, and extensive white matter changes with temporal cysts by imaging studies has been described in a particular ethnic group (Agarwals) in India. This disorder is very similar to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a newly characterized leukodystrophy whose molecular basis was recently shown to be mutations in a gene (KIAA0027) that has been renamed MLC1. Objective: To determine if this disorder among the Agarwals is due to mutations in MLC1 by a mutation screening study conducted on affected Agarwal patients. Methods: Genomic DNA from these Indian leukodystrophy patients was screened for mutations in the entire coding region, including the exon-intron boundaries, of the MLC1 gene. Results: Thirty-three affected individuals whose clinical and imaging presentations were consistent with MLC were screened. All were from northern India and included 31 known Agarwals, 1 non-Agarwal, and 1 adopted patient whose ethnicity is unknown. All 31 Agarwal patients tested positive for a homozygous insertion of a cytosine in exon 2. The adopted patient was homozygous for A157E. No mutation in the coding region was found in the non-Agarwal patient. Conclusions: Indian patients with megalencephaly and MRI changes that show extensive white matter changes with temporal cysts should raise suspicion for MLC. Members of the Agarwal ethnic group affected with the disorder present with a mildly progressive course and show a common mutation (320insC) in the MLC1 gene, suggesting a founder effect.