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

• Published in: Brain & development (Tokyo. 1979) Vol. 40; no. 7; pp. 587 - 591
• Main Authors: Matsumoto, Ayumi, Tulyeu, Janyerkye, Furukawa, Rieko, Watanabe, Chika, Monden, Yukifumi, Nozaki, Yasuyuki, Mori, Masato, Namekawa, Michito, Jimbo, Eriko F., Aihara, Toshinori, Yamagata, Takanori, Osaka, Hitoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2018
• Subjects: Aggregation; Alexander disease (AxD); Glial fibrillary acid protein (GFAP); Aggregation; Glial fibrillary acid protein (GFAP); Alexander disease (AxD)
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2018.03.002

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.