ヤマモト　トシユキ   Yamamoto Toshiyuki   山本　俊至    所属   医学部 医学科（東京女子医科大学病院）    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	CDKL5 alterations lead to early epileptic encephalopathy in both genders.
掲載誌名	正式名：Epilepsia 略　 称：Epilepsia ISSNコード：00139580/15281167
掲載区分	国外
巻・号・頁	52(10),pp.1835-1842
著者・共著者	Jao-Shwann Liang, Keiko Shimojima, Rumiko Takayama, Jun Natsume, Minobu Shichiji, Kyoko Hirasawa, Kaoru Imai, Tohru Okanishi, Seiji Mizuno, Akihisa Okumura, Midori Sugawara, Tomoshiro Ito, Hiroko Ikeda, Yukitoshi Takahashi, Hirokazu Oguni, Katsumi Imai, Makiko Osawa, Toshiyuki Yamamoto
発行年月	2011/10
概要	Purpose: Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. Methods: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. Key Findings: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. Significance: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.
DOI	10.1111/j.1528-1167.2011.03174.x