Balbi Pietro, Seri Marco, Ceccherini Isabella, Uggetti Carla, Casale Roberto, Fundarò Cira, Caroli Francesco, Santoro Lucio
Clinical Neurophysiology, Scientific Institute of Montescano IRCCS Fondazione S.Maugeri, via per Montescano, 27040, Montescano, PV, Italy.
J Neurol. 2008 Jan;255(1):24-30. doi: 10.1007/s00415-007-0654-0. Epub 2007 Nov 21.
Pathogenic, dominant, de novo missense mutations in the glial fibrillary acidic protein (GFAP) have been found in the three subtypes of infantile, juvenile and adult Alexander disease. Here we describe four members of an Italian family (32 to 66-yearsold, 2 women and 2 men) affected by adult Alexander disease, the least common and the most clinically variable form. Direct sequencing of all coding regions of the GFAP gene, neurological examination and brain MRI were performed. Two novel missense mutations were found involving two very close codons, c.[988C > G, 994G > A], leading to p.[Arg330Gly, Glu332Lys]. Clinically, two members exhibited pseudo-bulbar signs, gait ataxia and spasticity, one showed a severe cranial sensory symptomatology, and one subject was asymptomatic.Medulla and cervical cord atrophy was present in all of them on MRI. Although adult Alexander disease shows a wide clinical variability, a more frequent pattern can be identified characterized by bulbar or pseudo-bulbar signs, gait ataxia, and spasticity, and including on MRI medulla and cervical cord atrophy. Our findings also confirm that the clinical spectrum of adult Alexander disease includes cases without overt neurological involvement and with minimal brain MRI alterations.
在婴儿型、青少年型和成人型亚历山大病的三种亚型中均发现了胶质纤维酸性蛋白（GFAP）的致病性、显性、新发错义突变。本文描述了一个受成人型亚历山大病影响的意大利家庭的四名成员（年龄在32至66岁之间，2名女性和2名男性），成人型亚历山大病是最不常见且临床变异性最大的一种类型。对GFAP基因的所有编码区进行了直接测序，并进行了神经学检查和脑部磁共振成像（MRI）。发现了两个新的错义突变，涉及两个非常接近的密码子，即c.[988C > G, 994G > A]，导致p.[Arg330Gly, Glu332Lys]。临床上，两名成员表现出假性球麻痹体征、步态共济失调和痉挛，一名表现出严重的颅部感觉症状，一名受试者无症状。MRI显示他们所有人均存在延髓和颈髓萎缩。尽管成人型亚历山大病表现出广泛的临床变异性，但可以识别出一种更常见的模式，其特征为球麻痹或假性球麻痹体征、步态共济失调和痉挛，且MRI显示包括延髓和颈髓萎缩。我们的研究结果还证实，成人型亚历山大病的临床谱包括无明显神经受累且脑部MRI改变最小的病例。
