Department of Pediatrics, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Department of Neuroscience, Imaging and Clinical Science, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy; Neurology Clinic, Epilepsy Center, "SS Annunziata" Hospital of Chieti, Chieti, Italy; Behavioral Neurology and Molecular Neurology Units, Center for Advanced Studies and Technology - CAST-, University G. d'Annunzio of Chieti-Pescara, Italy.
Seizure. 2024 Jul;119:3-11. doi: 10.1016/j.seizure.2024.04.019. Epub 2024 Apr 23.
The proline-rich transmembrane protein 2 (PRRT2) is a synaptic protein involved in neurotransmitter vesicle release. PRRT2 protein is highly expressed in the cerebellum, cerebral cortex, basal ganglia, and hippocampus. Variants in PRRT2 have been identified as a cause of several neurological disorders, including epilepsy, movement disorders, and headache.
We report two families carrying two distinct PRRT2 mutations showing childhood onset of movement disorders, headache, and epilepsy. Demographics, clinical, EEG, neuroimaging, and genetic sequencing study data were collected. A systematic review of the literature was also performed to dissect the most frequently reported PRRT2-associated epileptic phenotypes.
two variants in PRRT2 gene (NM_145239.3:c718C>T, p.Arg240Ter; c.649dupC, p.Arg217Profs*8) were identified. The two variants altered the same extracellular domain of PRRT2. The de novo PRRT2 mutation (c718C>T, p.Arg240Ter) was related to multi-drug-resistant epilepsy. According to the literature, homozygous, biallelic variants and 16p11.2 deletions lead to PRRT2 haploinsufficiency and a more severe phenotype.
PRRT2 mutations can be associated with several epileptic phenotypes ranging from benign ASM-responsive form to more severe epileptic encephalopathies. Identifying PRRT2 variants in epilepsy patients may help achieve more personalized treatment approaches. However, phenotype-genotype correlations remain a challenge.
富含脯氨酸的跨膜蛋白 2（PRRT2）是一种参与神经递质囊泡释放的突触蛋白。PRRT2 蛋白在小脑、大脑皮层、基底节和海马体中高度表达。已经确定 PRRT2 中的变体是几种神经疾病的原因，包括癫痫、运动障碍和头痛。
我们报告了两个携带两种不同 PRRT2 突变的家族，这些突变表现为儿童期运动障碍、头痛和癫痫发作。收集了人口统计学、临床、EEG、神经影像学和遗传测序研究数据。还进行了系统的文献回顾，以剖析最常报道的 PRRT2 相关癫痫表型。
在 PRRT2 基因中发现了两个变体（NM_145239.3：c718C>T，p.Arg240Ter；c.649dupC，p.Arg217Profs*8）。这两个变体改变了 PRRT2 的相同细胞外结构域。新生 PRRT2 突变（c718C>T，p.Arg240Ter）与多药耐药性癫痫有关。根据文献，纯合子、双等位基因变体和 16p11.2 缺失导致 PRRT2 单倍不足和更严重的表型。
PRRT2 突变可与几种癫痫表型相关，从良性 ASM 反应形式到更严重的癫痫性脑病。在癫痫患者中鉴定 PRRT2 变体可能有助于实现更个性化的治疗方法。然而，表型-基因型相关性仍然是一个挑战。
