Aoki Y, Haginoya K, Munakata M, Yokoyama H, Nishio T, Togashi N, Ito T, Suzuki Y, Kure S, Iinuma K, Brenner M, Matsubara Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan.
Neurosci Lett. 2001 Oct 19;312(2):71-4. doi: 10.1016/s0304-3940(01)02139-5.
Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A alpha-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.
亚历山大病是一种罕见的进行性白质脑病，其标志是广泛积聚的罗森塔尔纤维。最常见的形式影响婴幼儿，其特征是中枢髓鞘形成进行性衰竭，通常导致成年前死亡。亚历山大病的确切诊断需要活检或尸检来证明罗森塔尔纤维的存在。然而，胶质纤维酸性蛋白（GFAP）基因编码区的错义突变最近与高比例经病理证实的病例相关。我们在此报告，一名表现出亚历山大病临床症状的10岁日本患者在GFAP保守的2Aα-螺旋结构域中存在一个从C到T的转换杂合突变，该突变预测了一个新的A244V氨基酸取代。在65名正常个体（130个等位基因）中未发现该核苷酸变化。这些结果进一步支持了GFAP突变在亚历山大病中的致病作用，并表明DNA测序可作为活检的替代诊断方法。
