title: Adult-onset Alexander disease : report on a family.
abstract: 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.
authors.affiliation: Clinical Neurophysiology, Scientific Institute of Montescano IRCCS Fondazione S.Maugeri, via per Montescano, 27040, Montescano, PV, Italy. pbalbi@fsm.it
authors.forename: Pietro
authors.initials: P
authors.lastname: Balbi
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.forename: Carla
authors.initials: C
authors.lastname: Uggetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Casale
authors.forename: Cira
authors.initials: C
authors.lastname: Fundarò
authors.forename: Francesco
authors.initials: F
authors.lastname: Caroli
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D038261:Alexander Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009128:Muscle Spasticity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D003062:Codon; D005819:Genetic Markers; D005904:Glial Fibrillary Acidic Protein