Wang P J, Hwu W L, Lee W T, Wang T R, Shen Y Z
Department of Pediatrics; National Taiwan University Hospital; Taipei, Republic of China.
Pediatr Neurol. 1997 Sep;17(2):125-8. doi: 10.1016/s0887-8994(97)00088-x.
The classic form of Pelizaeus-Merzbacher disease is a rare X-linked dysmyelinating disorder of the central nervous system in which mutations of the proteolipid protein gene have been reported since 1989. However, mutations in the proteolipid protein gene have been identified in only 10 to 25% of all cases of Pelizaeus-Merzbacher disease, which suggests that other genetic aberrations may be present. Recently, proteolipid protein gene overdosage was discovered to cause Pelizaeus-Merzbacher disease. By using comparative multiplex polymerase chain reaction and restriction fragment length polymorphism analysis, we confirmed the proteolipid protein gene duplication as the cause of Pelizaeus-Merzbacher disease in 4 patients from 3 Chinese families with Pelizaeus-Merzbacher disease with no detectable exonic mutations. These results support the hypothesis that proteolipid protein gene duplication may be a major cause of Pelizaeus-Merzbacher disease in all ethnic groups and also suggest that the molecular diagnosis of Pelizaeus-Merzbacher disease should therefore include duplication analysis of proteolipid protein gene.
佩利措伊斯-梅茨巴赫病的经典形式是一种罕见的X连锁中枢神经系统脱髓鞘疾病，自1989年以来已有关于其蛋白脂蛋白基因突变的报道。然而，在所有佩利措伊斯-梅茨巴赫病病例中，仅10%至25%的病例发现了蛋白脂蛋白基因突变，这表明可能存在其他基因畸变。最近，发现蛋白脂蛋白基因剂量过多可导致佩利措伊斯-梅茨巴赫病。通过使用比较多重聚合酶链反应和限制性片段长度多态性分析，我们证实了蛋白脂蛋白基因重复是3个患有佩利措伊斯-梅茨巴赫病的中国家庭中4例患者的病因，这些患者未检测到外显子突变。这些结果支持了蛋白脂蛋白基因重复可能是所有种族佩利措伊斯-梅茨巴赫病主要病因的假说，也表明佩利措伊斯-梅茨巴赫病的分子诊断因此应包括蛋白脂蛋白基因的重复分析。
