A clinical case of a patient with neonatal epilepsy at the age of 5 months, with impaired bone formation, early osteoporosis and frequent limb fractures is described. Panel sequencing confirmed by Sanger sequencing revealed two independent hereditary diseases - osteogenesis imperfect type 1, associated with a mutation in the COL1A1 gene (c.2010delT) and benign non-familial infantile seizures associated with a mutation in the PRRT2 gene (c.649dupC). A unique clinical case of a combination of these diseases is presented.
Описан клинический случай пациента с неонатальной эпилепсией в возрасте 5 мес жизни, с нарушением формирования костной ткани, ранним остеопорозом и частыми переломами конечностей. Методами панельного секвенирования и подтверждающего секвенирования по Сэнгеру выявлены две независимые наследственные болезни — несовершенный остеогенез 1-го типа, ассоциированный с мутацией в гене COL1A1 (с.2010delT), и доброкачественные несемейные инфантильные приступы, ассоциированные с мутацией в гене PRRT2 (c.649dupC). Представлен уникальный клинический случай сочетания данных заболеваний.

Mutations in the PRRT2 (proline-rich transmembrane protein 2) gene have been identified as the main cause of an expanding spectrum of disorders, including paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy, which places this gene at the border between epilepsy and movement disorders. The clinical spectrum has largely expanded to include episodic ataxia, hemiplegic migraine, and complex neurodevelopmental disorders in cases with biallelic mutations. Prior to the discovery of PRRT2 as the causative gene for this spectrum of disorders, the sensitivity of paroxysmal kinesigenic dyskinesia to anticonvulsant drugs regulating ion channel function as well as the co-occurrence of epilepsy in some patients or families fostered the hypothesis this could represent a channelopathy. However, recent evidence implicates PRRT2 in synapse functioning, which disproves the \"channel hypothesis\" (although PRRT2 modulates ion channels at the presynaptic level), and justifies the classification of these conditions as synaptopathies, an emerging rubric of brain disorders. This review aims to provide an update of the clinical and pathophysiologic features of PRRT2-associated disorders.

To identify the causative gene of autosomal dominant paroxysmal kinesigenic dyskinesia and benign familial infantile seizures (PKD/BFIS) in a large Chinese family and explore the potential pathogenic mechanism of a PRRT2 (proline-rich transmembrane protein 2) variant.
Genetic testing was performed via whole exome sequencing. Western blotting and immunofluorescence were used to analyze the protein expression level and subcellular localization of the PRRT2 mutant in HeLa cells and N2A cells. Coimmunoprecipitation was conducted to investigate the interaction of the PRRT2 mutant with syntaxin 1B (STX1B).
In a large Chinese family with autosomal dominant PKD/BFIS showing wide phenotypic heterogeneity, including patients suffering from PKD, BFIS, or epilepsy and asymptomatic variant carriers, a c.621dupA variant in PRRT2 was identified in the proband and was shown to cosegregate with the phenotype in this family. This variant results in premature termination at codon 224, producing a truncated protein (p.Ser208Ilefs*17) in which the two conserved hydrophobic segments and the cytoplasmic loop are missing. Both the expression and subcellular localization of PRRT2 are strongly affected by the c.621dupA variant. In addition, we found that PRRT2 directly interacts with STX1B, a SNARE protein critical for neurotransmitter release, whereas the truncated variant p.Ser208Ilefs*17 lacking the helix-loop-helix domain fails to bind to STX1B.
Our findings identified a PRRT2 variant in a family with PKD/BFIS and confirmed STX1B as a new binding partner of PRRT2, which suggested that the loss of the interaction between PRRT2 and STX1B may contribute to the pathogenesis of PKD/BFIS.

Benign familial infantile seizure (BFIS) and paroxysmal kinesigenic dyskinesia (PKD) are autosomal-dominant inherited self-limited neurological disorders. BFIS is characterized by clusters of epileptic seizures in infancy while, in some cases, infantile seizures and adolescent-onset paroxysmal kinesigenic choreoathetosis co-occurred, which is called infantile convulsions and choreoathetosis (ICCA) syndrome. We and other researchers have reported the proline-rich transmembrane protein 2 (PRRT2) as the causative gene of PKD. We and our collaborators also identified PRRT2 mutations in ICCA and other phenotypes. Here we collected two BFIS families of Chinese Han origin. The linkage analysis has mapped the BFIS-causing locus to 16p12.1-q12.2, where PRRT2 is located. We then performed mutation analysis of PRRT2 by direct sequencing and identified c.649-650insC mutation in all BFIS patients. We also noticed that paroxysmal diseases (such as BFIS, PKD and ICCA) with PRRT2 mutations, instead of other forms, share some characteristics like being responded well to anti-epiletic treatment, we thus suggest to name them as PRRT2-related paroxysmal diseases (PRPDs) in order to assist clinical diagnosis and treatment.