A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures

Jacqueline G. Lu, Juliet Bishop, Sarah Cheyette, Igor B. Zhulin, Su Guo, Nara Sobreira, Steven E. Brenner

Research output: Contribution to journalArticle

Abstract

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, NM-001256442:exon3:c. C959T/NP-660282.2: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.

Original languageEnglish (US)
Article numbera002287
JournalCold Spring Harbor molecular case studies
Volume4
Issue number1
DOIs
StatePublished - Feb 1 2018

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Exome
Seizures
Pluripotent Stem Cells
Movement Disorders
Nervous System Diseases
Consciousness
Proline
Fathers
Alanine
Siblings
Animal Models
Mothers
Amino Acids
Grandparents
Familial paroxysmal dystonia
Proteins

ASJC Scopus subject areas

  • Medicine(all)

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A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. / Lu, Jacqueline G.; Bishop, Juliet; Cheyette, Sarah; Zhulin, Igor B.; Guo, Su; Sobreira, Nara; Brenner, Steven E.

In: Cold Spring Harbor molecular case studies, Vol. 4, No. 1, a002287, 01.02.2018.

Research output: Contribution to journalArticle

Lu, Jacqueline G. ; Bishop, Juliet ; Cheyette, Sarah ; Zhulin, Igor B. ; Guo, Su ; Sobreira, Nara ; Brenner, Steven E. / A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. In: Cold Spring Harbor molecular case studies. 2018 ; Vol. 4, No. 1.
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