A Novel &lt;i&gt;GFAP&lt;/i&gt; Mutation and Disseminated White Matter Lesions: Adult Alexander Disease?

Brockmann, Knut; Meins, Moritz; Taubert, Angelika; Trappe, Ralf Ulrich; Grond, Martin; Hanefeld, F.

doi:10.1159/000072507

Cited by 25 publications

(15 citation statements)

References 13 publications

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“…We tentatively classify both D157N and E223Q as polymorphisms by their presence in normal parents, but incomplete penetrance is equally plausible. E223Q was previously found in a putative Alexander disease patient, 43 and the site is highly conserved among intermediate filaments (see Table 6). However, interpretation of both MRI and clinical signs for that patient are complicated by his alcoholism and hypertension, and the patient's mother carries the same change.…”

Section: Glial Fibrillary Acidic Protein Polymorphismsmentioning

confidence: 85%

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

Johnson

Salomons

et al. 2005

Annals of Neurology

236

291

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Alexander disease is a progressive, usually fatal neurological disorder defined by the widespread and abundant presence in astrocytes of protein aggregates called Rosenthal fibers. The disease most often occurs in infants younger than 2 years and has been labeled a leukodystrophy because of an accompanying severe myelin deficit in the frontal lobes. Later onset forms have also been recognized based on the presence of abundant Rosenthal fibers. In these cases, clinical signs and pathology can be quite different from the infantile form, raising the question whether they share the same underlying cause. Recently, we and others have found pathogenic, de novo missense mutations in the glial fibrillary acidic protein gene in most infantile patients examined and in a few later onset patients. To obtain further information about the role of glial fibrillary acidic protein mutations in Alexander disease, we analyzed 41 new patients and another 3 previously described clinically, including 18 later onset patients. Our results show that dominant missense glial fibrillary acidic protein mutations account for nearly all forms of this disorder. They also significantly expand the catalog of responsible mutations, verify the value of magnetic resonance imaging diagnosis, indicate an unexpected male predominance for the juvenile form, and provide insights into phenotype-genotype relations.

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Section: Glial Fibrillary Acidic Protein Polymorphismsmentioning

confidence: 85%

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

Johnson

Salomons

et al. 2005

Annals of Neurology

236

291

View full text Add to dashboard Cite

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“…Other GFAP mutations in cases showing the adult form of Alexander disease have been reported (Table 1) [8,[10][11][12][13][14][15][16]. The onset age ranged from 21 to over 50.…”

Section: Discussionmentioning

confidence: 97%

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein

et al. 2007

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Glial fibrillary acidic protein (GFAP) mutation has been reported in Alexander disease. We report a patient with the adult form of Alexander disease who shows a novel mutation in GFAP. This case presented with progressive dysarthria, dysphagia and spastic gait on the right side. Brain and spinal cord MRI showed marked atrophy of the medulla oblongata and spinal cord. Abnormal high signal intensities in the ventral medulla oblongata were detected bilaterally. There were no white matter lesions or contrast enhancing lesions. Recently, there have been reports of patients with a juvenile form of Alexander disease presenting with atrophy or signal abnormalities of the medulla or spinal cord. Atrophy of the medulla and spinal cord have specifically been described as suggestive of Alexander disease [1]. Sequence analysis of the GFAP gene of this patient showed a heterozygous c.221T>C mutation, predicting a p.M74T amino acid change. In all patients suspected of Alexander disease on the basis of MRI findings, GFAP analysis is necessary to confirm the diagnosis.

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“…However, the recent discovery of healthy relatives of patients affected by AxD carrying identical GFAP mutations, [2,5,24,25,29], as well as the serendipitous preclinical ascertainment by means of MRI in genetically proven AxD cases [13,25,35], strongly supports the view that AxD displays a wide spectrum of clinical expression, ranging from the severe and rapidly progressive infantile forms to those with minimal MRI abnormalities without neurological impairments. Some authors [13,20] proposed the possible presence of a 'forme fruste' of AxD.…”

Section: Discussionmentioning

confidence: 98%

The clinical spectrum of late-onset Alexander disease: a systematic literature review

et al. 2010

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Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

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A Novel <i>GFAP</i> Mutation and Disseminated White Matter Lesions: Adult Alexander Disease?

Cited by 25 publications

References 13 publications

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein

The clinical spectrum of late-onset Alexander disease: a systematic literature review

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