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A Novel Truncation Mutation of the PRRT 2 Gene Resulting in a 16‐Amino‐Acid Protein Causes Self‐inducible Paroxysmal Kinesigenic Dyskinesia
Author(s) -
Kita Makoto,
Kuwata Yasuhiro,
Murase Nagako,
Akiyama Yuichi,
Usui Takeshi
Publication year - 2017
Publication title -
movement disorders clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 18
ISSN - 2330-1619
DOI - 10.1002/mdc3.12500
Subject(s) - paroxysmal dyskinesia , nonsense mutation , haploinsufficiency , medicine , genetics , dyskinesia , mutation , missense mutation , phenotype , gene , biology , disease , parkinson's disease
Paroxysmal kinesigenic dyskinesia ( PKD ) is a sporadic or autosomal‐dominant, hereditary disorder characterized by brief, recurrent attacks of involuntary movements triggered by sudden, voluntary movement that generally develops during childhood and adolescence and is typically treated with carbamazepine. The proline‐rich transmembrane protein 2 ( PRRT 2 ) gene contains 4 exons that encode 340 amino acids as the major isoform, and recent research has identified PRRT 2 as the primary causative gene in PKD , benign familial infantile epilepsy ( BFIE ), and infantile convulsions with PKD ( PKD / IC ). Here, the authors report the phenotype of a family with a novel p.E16X (c.46G>T) nonsense mutation of the PRRT 2 gene that lacked almost a full allele. In this family, none of the individuals in the pedigree exhibited evidence of cognitive impairment: the elder brother had PKD / IC with migraine; the younger brother had PKD with ataxia; the father had PKD ; both siblings experienced a sensory aura; and all 3 had a history of febrile seizures. This is the first report of a short nonsense mutation in PRRT 2 and indicates that the manifestations of the disease, including other mutations to date, can be explained by haploinsufficiency and that 1 intact PRRT 2 allele can allow normal cognitive development.