title: Myofibrillogenesis regulator 1 gene (MR-1) mutation in an Omani family with paroxysmal nonkinesigenic dyskinesia.
abstract: Two recurrent missense mutations (c.20C>T: A7V; c.26C>T: A9V) in the gene encoding the myofibrillogenesis regulator 1 (MR-1) have been shown to cause autosomal dominant paroxysmal nonkinesigenic dyskinesia (PNKD) in 13 families of primarily European ancestry. Here we report an Omani PNKD family with seven affected family members and autosomal dominant inheritance. Our linkage analysis provided consistent positional evidence that the MR-1 gene could be the responsible disease gene. Sequence analysis identified a MR-1 missense mutation (c.20C>T; A7V) in the affected family members, whereas it was not present in five unaffected family members and 129 population controls. Taking into account that previous haplotype analyses did not reveal evidence for common founders among several PNKD families, our present findings strengthen three implications: (1) autosomal dominant PNKD seems to be a homogenous disorder, for which the MR-1 gene is the major disease gene; (2) mainly two recurrent MR-1 missense mutations (57% V7, 43% V9) account for the genetic variance of familial PNKD; (3) it supports current evidence that some of the recurrent MR-1 mutations may have arisen independently by de novo mutation at functionally convergent key sites of the brain-specific MR-1L isoform.
authors.affiliation: Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Department of Neurology, Charité University Medicine, Berlin, Germany, and Department of Neurology, The Royal Hospital, Muscat, Oman.
authors.forename: Anne
authors.initials: A
authors.lastname: Hempelmann
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Shanmugakonar
authors.initials: S
authors.lastname: Muralitharan
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
mesh_terms: D002819:Chorea / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009850:Oman
chemical_list: D009124:Muscle Proteins; C495444:PNKD protein, human