Infantile Alexander Disease: A GFAP Mutation in Monozygotic Twins and Novel Mutations in Two Other Patients[*]

Abstract

Alexander disease (AD) is a rare disorder of cerebral white matter due to a dysfunction of astrocytes. The most common infantile form presents as a megalencephalic leukodystrophy. Recently, heterozygous de novo mutations in the glial fibrillary acidic protein gene (GFAP) have been demonstrated to be associated with AD. We report heterozygous mutations in GFAP in 5 patients, including a pair of monozygotic twins, with clinical and neuroradiological features of infantile AD. Novel mutations were detected affecting nucleotides 304 T → C (L97 P) and 730 G → C (R239 P) in two other patients. None of the parents of our patients carried the mutations stressing dominant de novo mutations as the cause of AD. The presence of an identical mutation 250 G → A (R79 H) in both monozygotic twins with infantile AD points to the origin of these GFAP mutations in germ cells or very early postzygotic stages.

Key words

GFAP Gene - Glial Fibrillary Acidic Protein - Alexander Disease - Leukodystrophy

1 M. M. and K. B. contributed equally to this work

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1 M. M. and K. B. contributed equally to this work