A common mutation and a novel mutation in Japanese patients with van der Knaap disease
A common mutation and a novel mutation in Japanese patients with van der Knaap disease
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DOI：
10.1007/s10038-003-0085-4
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发表时间：
2003-12-01
影响因子：
3.5
通讯作者：
Oba, H
中科院分区：
文献类型：
--
作者：
Tsujino, S;Kanazawa, N;Oba, H
货车der Knaap病，又称巨脑白质脑病伴皮质下囊肿（MLC），是一种常染色体隐性遗传疾病，临床表现为大头畸形、共济失调、痉挛和智力下降。磁共振成像（MRI）显示脑肿胀，弥漫性白质异常和皮质下囊肿，特别是在前颞区。最近，MLC 1基因被确定为负责这种疾病的基因，并在几个患者中描述了该基因的突变。我们在分子遗传学水平上研究了3例日本货车der Knaap病患者。其中两个是纯合子的一个先前描述的突变，S93 L，和一个是复合杂合子的S93 L和一个新的突变，452- 468 del +g，这导致移码与提前终止密码子。结合我们的数据与以前的报告，使我们能够估计这种疾病的分子遗传基础，在7名日本患者。总之，在7名患者中的6名（85.7%）患者中观察到至少一个等位基因中的S93 L，并且14个等位基因中的10个（71.4%）具有该突变。因此，S93 L似乎在日本货车der Knaap病患者中相当常见，对从白细胞中分离的DNA中的这种突变的分析将提供日本患者中这种疾病的简单和精确的诊断。
Van der Knaap disease, or megalencephalic leukoencephalopathy with subcortical cysts (MLC), is an autosomal recessive disorder clinically characterized by macrocephaly, ataxia, spasticity, and mental decline. Magnetic resonance imaging (MRI) shows swollen brain with diffuse white-matter abnormalities and subcortical cysts, particularly in the anterior-temporal region. Recently, the MLC1 gene was identified as the gene responsible for this disorder, and mutations in this gene were described in several patients. We studied three Japanese patients with van der Knaap disease at the molecular genetic level. Two of them were homozygous for a previously-described mutation, S93L, and one was a compound heterozygote for S93L and a novel mutation, 452-468del+g, which leads to frameshift with a premature termination codon. Combining our data with previous reports allowed us to estimate the molecular genetic basis of this disorder in seven Japanese patients. In summary, S93L was observed in six of seven (85.7%) patients at least in one allele, and ten of 14 (71.4%) alleles had this mutation. Therefore, S93L appears to be fairly frequent in Japanese patients with van der Knaap disease, and analysis for this mutation in DNA isolated from leukocytes would provide for an easy and precise diagnosis of this disorder in Japanese patients.