@article {629,
	title = {A novel  pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures.},
	journal = {Cold Spring Harb Mol Case Stud},
	volume = {4},
	year = {2018},
	month = {2018 02},
	abstract = {<p>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  (proline-rich transmembrane protein), a gene with a function in synaptic regulation that remains poorly understood. Here, we report the discovery of a novel  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  pathogenic variants, we carried out whole-exome sequencing in the proband and her affected paternal grandfather. This led to the discovery of a novel  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  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  and the significance of this variant in regulating neural development and/or function.</p>},
	keywords = {Amino Acid Sequence, Base Sequence, Child, Chromosome Segregation, Conserved Sequence, Dystonia, Epilepsy, Benign Neonatal, Evolution, Molecular, Family, Female, Humans, Infant, Inheritance Patterns, Male, Membrane Proteins, Mutation, Nerve Tissue Proteins, Pedigree},
	issn = {2373-2873},
	doi = {10.1101/mcs.a002287},
	author = {Lu, Jacqueline G and Bishop, Juliet and Cheyette, Sarah and Zhulin, Igor B and Guo, Su and Sobreira, Nara and Brenner, Steven E}
}
