title: Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences.
abstract: Heterozygous mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We report a consanguineous Italian family with BFIS/PKD phenotype that contained 14 living members with 6 affected individuals (four men, ranging in age from 6-44 years). We identified the reported c.649dupC (p.Arg217ProfsX8) mutation of PRRT2 gene that cosegregated with the disease and was not observed in 100 controls of matched ancestry. Four patients with BFIS phenotype were heterozygous for this mutation, including the consanguineous parents of the two affected brothers with more severe phenotypes of BFIS/PKD--mental retardation, episodic ataxia, and absences--who were the only individuals to carry a homozygous c.649dupC mutation. This family provides strong evidence that homozygous PRRT2 mutations give rise to more severe clinical disease of mental retardation, episodic ataxia, and absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations. Moreover, it suggests an additive effect of double dose of the genetic mutation and underscores the complexity of the phenotypic consequences of mutations in this gene.
authors.affiliation: Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarantino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viri
authors.forename: Laura
authors.initials: L
authors.lastname: Mumoli
authors.forename: Monica
authors.initials: M
authors.lastname: Gagliardi
authors.forename: Antonino
authors.initials: A
authors.lastname: Romeo
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Grazia
authors.initials: G
authors.lastname: Annesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
mesh_terms: D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D002648:Child; D002819:Chorea / Q000150:complications / Q000235:genetics*; D020936:Epilepsy, Benign Neonatal / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human