Hodes M E, Blank C A, Pratt V M, Morales J, Napier J, Dlouhy S R
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA.
Am J Med Genet. 1997 Mar 17;69(2):121-5.
We report a G-->A transition at nucleotide 431 of the proteolipid protein gene (PLP) results in a nonsense codon in a family with an unusual form of Pelizaeus-Merzbacher disease (PMD). The mutation, which creates a second AluI restriction site, results in a nonsense mutation in PLP. The clinical picture resembles somewhat that of X-linked spastic paraplegia (SPG). It differs from this and both the classical and connatal forms of PMD in that it is relatively mild in form, onset is delayed beyond age 2 years, nystagmus is absent, tremors are prominent, mental retardation is not severe, some patients show dementia or personality disorders, the disease is progressive rather than static in some, and several females show signs of disease. The nonsense mutation, which is in exon 3B, should block the synthesis of normal PLP but spare DM20, the isoform whose persistence has been associated with mild forms of PLP-associated disease in both humans and mice.
我们报告了在一个患有罕见形式佩利措伊斯-梅茨巴赫病（PMD）的家族中，蛋白脂质蛋白基因（PLP）第431位核苷酸发生G→A转换，导致产生一个无义密码子。该突变产生了第二个AluI限制性酶切位点，导致PLP出现无义突变。临床症状 somewhat 类似于X连锁痉挛性截瘫（SPG）。它与SPG以及经典型和先天性PMD的不同之处在于，其症状相对较轻，发病延迟至2岁以后，无眼球震颤，震颤明显，智力发育迟缓不严重，一些患者表现出痴呆或人格障碍，该疾病在某些患者中呈进行性而非静止性，并且有几名女性表现出疾病迹象。位于外显子3B的无义突变应会阻断正常PLP的合成，但保留DM20，在人类和小鼠中，该异构体的持续存在与轻度形式的PLP相关疾病有关。 （注：原文中“somewhat”翻译为“有点，稍微”，放在这里语义不太通顺，推测原文可能有误，暂保留原文形式。）
