TY - JOUR
T1 - A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease
AU - Aoki, Yoko
AU - Haginoya, Kazuhiro
AU - Munakata, Mitsutoshi
AU - Yokoyama, Hiroyuki
AU - Nishio, Toshiyuki
AU - Togashi, Noriko
AU - Ito, Tatsuo
AU - Suzuki, Yoichi
AU - Kure, Shigeo
AU - Iinuma, Kazuie
AU - Brenner, Michael
AU - Matsubara, Yoichi
N1 - Funding Information:
We thank Kumi Narita for technical assistance. This study was supported by Ministry of Education, Culture, Sports, Science, and Technology in Japan.
PY - 2001/10/19
Y1 - 2001/10/19
N2 - Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A α-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.
AB - Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A α-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.
KW - Alexander disease
KW - Glial fibrillary acidic protein
KW - Leukoencephalopathy
KW - Mutations
KW - Positron emission tomography
KW - Single photon emission computerized tomography
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U2 - 10.1016/S0304-3940(01)02139-5
DO - 10.1016/S0304-3940(01)02139-5
M3 - Article
C2 - 11595337
AN - SCOPUS:0035914004
VL - 312
SP - 71
EP - 74
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -