Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
PLoS One. 2023 Apr 26;18(4):e0284924. doi: 10.1371/journal.pone.0284924. eCollection 2023.
Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with NPRL3 variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various NPRL3 variants and explored the effect of NPRL3 variant on mRNA.
We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative-polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals.
Patients with NPRL3: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe/temporal lobe), different seizure times (day/night) and frequencies (monthly/seldom/every day), different therapeutic effects (refractory epilepsy/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different NPRL3 variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes.
The clinical features of FFEVF varied, and auxiliary inspection was atypical. NPRL3: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.
家族性局灶性癫痫伴可变病灶（FFEVF）是一种罕见的局灶性癫痫综合征，与 NPRL3 变异相关。然而，中国相关报道较少。本研究旨在分析中国 FFEVF 患者的临床特征，进一步了解不同 NPRL3 变异的差异，并探讨 NPRL3 变异对 mRNA 的影响。
对一个 FFEVF 家系（4 名患者，1 名健康成员）进行了全面检查：病史询问、头颅磁共振成像（MRI）、脑电图（EEG）和全外显子测序。将他们的临床特征与已发表的其他 FFEVF 患者的特征进行了比较。采用实时定量聚合酶链反应（q-PCR）和反转录（RT）-PCR 对 mRNA 剪接变化进行定量和定性分析，并与健康个体进行比较。
NPRL3：c.1137dupT 变异患者的发病年龄范围较广（4 个月至 31 岁），发作类型多样，病灶部位（额叶/颞叶）可变，发作时间（白天/夜间）和频率（每月/很少/每天）不同，治疗效果不同（耐药性癫痫/几乎无发作），MRI 正常，脑电图异常（痫样放电，慢波）。不同 NPRL3 变异的表型谱相似或不同。实时 qPCR 显示患者与健康个体之间的 mRNA 相对量存在显著差异。与健康个体相比，RT-PCR 观察到患者的异常剪接。尽管存在相同的基因突变，但不同的家庭成员的 mRNA 剪接不同，可能导致不同的表型。
FFEVF 的临床特征多种多样，辅助检查不典型。NPRL3：c.1137dupT 可能改变 mRNA 的相对数量并导致异常剪接，从而在不同的家庭成员中产生不同的表型。
