講演情報
[OE3-5]KCNH5新規de novo変異を認めた難治性てんかん脳症の一例
○光武 明彦1,2, 松川 敬志1, 石浦 浩之1, 三井 純3, 原田 広顕4, 藤尾 圭志4, 藤代 準5, 森 墾6, 森下 真一7, 辻 省次8, 戸田 達史1 (1.東京大学大学院医学系研究科 脳神経医学専攻神経内科学, 2.国際医療福祉大学三田病院 脳神経内科, 3.東京大学大学院医学系研究科 分子神経学, 4.東京大学医学部附属病院 アレルギーリウマチ内科, 5.東京大学医学部附属病院 小児外科, 6.自治医科大学 放射線医学講座, 7.東京大学大学院 新領域創成科学研究科メディカル情報生命専攻, 8.国際医療福祉大学 ゲノム医学研究所)
[Objective] We describe a novel de novo KCNH5 variant in a patient with epileptic encephalopathy. [Methods] Trio exome sequencing was performed. Candidate de novo variants were selected such that the number of alternative allele reads is at least 30% in the proband against reliable homozygous references in each parent. Candidates were validated by Sanger sequencing. [Results] The patient is a 24-year-old man. Developmental delay was noticed at the age of 9 months. Brain MRI showed cerebral atrophy and cerebellar hypoplasia. Epilepsy and regression worsened afterward, and he became bedridden. He was referred for a genetic diagnosis. We identified three de novo variants including a heterozygous p.K214Q variant in KCNH5. This variant was at a conserved position across vertebrates and not registered in databases. CADD Phred score was 26.0. Allele frequencies of the other two variants were high (0.32 and 0.13 in ToMMo). Other candidates were not detected from the conventional exome sequencing. [Discussion] Although KCNH5 has not been established as a causative gene for a specific disease, a heterozygous p.R327H variant in KCNH5 was reported in a case of epileptic encephalopathy by Veeramah (2013). Furthermore, Kv10.1 encoded by KCNH1 and Kv10.2 encoded by KCNH5 belong to the EAG K+ channel family. K214 residue in Kv10.2 corresponds to K217 in Kv10.1, and p.K217N has been described as pathogenic for Temple-Baraitser syndrome. Taken together, the p.K214Q variant is considered pathogenic. This study supports the notion that KCNH5 is a causative gene for epileptic encephalopathy.