A case of severe Alexander disease with de novo c. 239 T > C, p.(F80S), in GFAP

• DOI: 10.1016/j.braindev.2018.03.002
• Publication Date: 2018-03-21T21:06:42Z
• Authors: Ayumi Matsumoto; Janyerkye Tulyeu; Rieko Furukawa; Chika Watanabe; Yukifumi Monden; Yasuyuki Nozaki; Masato Mori; Michito Namekawa; Eriko F. Jimbo; Toshinori Aihara; Takanori Yamagata; Hitoshi Osaka
• Keywords: Male; Cytoplasm; Brain; Transfection; 3. Good health; 03 medical and health sciences; Fatal Outcome; 0302 clinical medicine; Cell Line, Tumor; Child, Preschool; Glial Fibrillary Acidic Protein; Mutation; Humans; Alexander Disease; HeLa Cells

Alexander disease (AxD) is a progressive neurodegenerative disease caused by a mutation in the glial fibrillary acid protein (GFAP) gene. A 4-year-old boy presented several times with hemiclonic seizures with eye deviation for a few minutes at 28 days after birth. Electroencephalogram showed independent sharp waves in the right and left temporal area. Magnetic resonance imaging showed high intensity T1-weighted images in the white matter of the frontal lobe and basal ganglia. He showed no head control at 4 years of age, and his weight gain was insufficient. He did not show macrocephaly. At 4 years of age, he died of bacterial pneumonia and septic shock. He was diagnosed with AxD, and direct sequencing revealed a de novo known mutation, c. 239 T > C, p.(F80S), in GFAP. Hela and U2-OS cells transfected with GFAP cDNA with c. 239 T > C showed dot-like cytoplasmic aggregation, similar to R239C, a common mutation found in severe infantile AxD. Aggregation in the cytoplasm caused by a GFAP mutation is a hallmark of AxD. Although there is only one previous report of a patient with an F80S mutation, our data support that F80S can cause the severe, infantile form of AxD.