A Novel Truncation Mutation of the Gene Resulting in a 16-Amino-Acid Protein Causes Self-inducible Paroxysmal Kinesigenic Dyskinesia.

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 () gene contains 4 exons that encode 340 amino acids as the major isoform, and recent research has identified 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 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 and indicates that the manifestations of the disease, including other mutations to date, can be explained by haploinsufficiency and that 1 intact allele can allow normal cognitive development.