シモジマ　ケイコ   Shimojima Keiko   下島　圭子    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Loss-of-function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy.
掲載誌名	正式名：Journal of Human Genetics
巻・号・頁	56(8),pp.561-565
著者・共著者	Keiko Shimojima, Midori Sugawara, Minobu Shichiji, Souichi Mukaida, Rumiko Takayama, Katsumi Imai, Toshiyuki Yamamoto
発行年月	2011/08
概要	Microarray-based comparative genomic hybridization analysis identified a 737-kb microdeletion of Xq11.1, including the cell division cycle 42 guanine nucleotide exchange factor (GEF)-9 gene (ARHGEF9), encoding collybistin, which has a pivotal role in formation of postsynaptic glycine and γ-aminobutyric acid receptor clusters, in a male patient with severe mental retardation and epilepsy. No overlapping deletion with this was identified in the database of genomic copy number variations. A cohort study of ARHGEF9 nucleotide sequence identified a nonsense mutation in another male patient with severe mental retardation and epilepsy. This mutation affects one of the three transcript variants of ARHGEF9, which was confirmed to be expressed in the brain by reverse transcription-PCR. Although this nonsense mutation was shared with the patient's mother, it was not observed in 100 normal individuals. Both male patients suffered epileptic seizures after 1 year of age. Brain magnetic resonance imaging revealed mild frontal atrophy in the first patient and right frontal polymicrogyria in the second patient. Three previously reported mutations of ARHGEF9 consisted of a missense mutation in a male patient with hyperekplexia and two chromosomal disruptions in two female patients. The common phenotypic effects of all ARHGEF9 mutations were mental retardation and epilepsy. Therefore, ARHGEF9 is likely to be responsible for syndromic X-linked mental retardation associated with epilepsy.
DOI	10.1038