Zou Dongfang, Qin Bing, Wang Jie, Shi Yiwu, Zhou Peng, Yi Yonghong, Liao Jianxiang, Lu Xinguo
Epilepsy Center and Department of Neurology, Shenzhen Children's Hospital, Shenzhen, China.
Department of Neurology, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Mol Neurosci. 2022 Mar 30;15:795840. doi: 10.3389/fnmol.2022.795840. eCollection 2022.
mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between and epilepsy has not been defined.
Trios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes.
Five hemizygous missense mutations were identified in five males with partial epilepsy and antecedent febrile seizures without intellectual disability or other developmental abnormalities. The mutations did not present in the controls of general populations with an aggregate frequency significantly higher than that in the control populations. Previously, intellectual disability-associated mutations were genomic rearrangements and CCG repeat expansion mutations mostly, whereas the mutations associated with partial epilepsy were all missense. Missense mutations associated with epilepsy fell into the regions from N-terminal to the nuclear localization signal 1 (NLS1), while ASD-associated missense mutations fell in the regions from NLS1 to C-terminal.
is potentially a candidate causative gene of X-link partial epilepsy with antecedent febrile seizures. The genotype-phenotype correlation and molecular sub-regional effect of help in explaining the mechanisms underlying phenotypic variations.
突变与X连锁智力发育障碍109相关，在男性中与自闭症谱系障碍（ASD）相关。 与癫痫之间的关系尚未明确。
对372例无后天病因的部分性（局灶性）癫痫无关病例（家庭）进行基于三联体的全外显子组测序。
在5例患有部分性癫痫且有热性惊厥病史但无智力残疾或其他发育异常的男性中鉴定出5个半合子错义突变。这些突变在一般人群对照中未出现，其总体频率显著高于对照人群。此前，与智力残疾相关的突变大多是基因组重排和CCG重复扩增突变，而与部分性癫痫相关的突变均为错义突变。与癫痫相关的错义突变位于从N端到核定位信号1（NLS1）的区域，而与ASD相关的错义突变位于从NLS1到C端的区域。
可能是伴有热性惊厥病史的X连锁部分性癫痫的候选致病基因。 的基因型-表型相关性和分子亚区域效应有助于解释表型变异的潜在机制。
