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首页> 美国卫生研究院文献>Cold Spring Harbor Molecular Case Studies >A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures
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A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures

机译：阵发性运动致动障碍和良性家族性婴儿癫痫发作家族中的新型PRRT2致病变异

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摘要

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent attacks of dyskinetic movements without alteration of consciousness that are often triggered by the initiation of voluntary movements. Whole-exome sequencing has revealed a cluster of pathogenic variants in PRRT2 (proline-rich transmembrane protein), a gene with a function in synaptic regulation that remains poorly understood. Here, we report the discovery of a novel PRRT2 pathogenic variant inherited in an autosomal dominant pattern in a family with PKD and benign familial infantile seizures (BFIS). After targeted Sanger sequencing did not identify the presence of previously described PRRT2 pathogenic variants, we carried out whole-exome sequencing in the proband and her affected paternal grandfather. This led to the discovery of a novel PRRT2 variant, :exon3:c.C959T/:p.A320V, altering an evolutionarily conserved alanine at the amino acid position 320 located in the M2 transmembrane region. Sanger sequencing further confirmed the presence of this variant in four affected family members (paternal grandfather, father, brother, and proband) and its absence in two unaffected ones (paternal grandmother and mother). This newly found variant further reinforces the importance of PRRT2 in PKD, BFIS, and possibly other movement disorders. Future functional studies using animal models and human pluripotent stem cell models will provide new insights into the role of PRRT2 and the significance of this variant in regulating neural development and/or function.
机译：阵发性运动原性运动障碍（PKD）是一种罕见的神经系统疾病，其特征是运动性运动反复发作而无意识改变，这通常是由自愿运动引发的。全外显子测序揭示了PRRT2（富含脯氨酸的跨膜蛋白）中的一系列致病变异体，该基因在突触调控中具有功能，目前尚不清楚。在这里，我们报告发现一个新的PRRT2致病变异的发现，该家族在具有PKD和良性家族性婴儿惊厥（BFIS）的家庭中以常染色体显性模式遗传。在针对性的Sanger测序无法确定先前描述的PRRT2病原体变异的存在之后，我们在先证者及其患病的祖父中进行了全外显子组测序。这导致发现新颖的PRRT2变体：exon3：c.C959T /：p.A320V，从而改变了位于M2跨膜区域的氨基酸位置320处的进化保守的丙氨酸。 Sanger测序进一步证实了该变异体存在于四个受影响的家庭成员（祖父，祖父，父亲，兄弟和先证者）中，而在两个未受影响的家庭成员（父亲，祖母和母亲）中不存在。这个新发现的变体进一步增强了PRRT2在PKD，BFIS和其他运动障碍中的重要性。未来使用动物模型和人类多能干细胞模型进行的功能研究将为PRRT2的作用以及该变体在调节神经发育和/或功能中的意义提供新的见解。

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