title: FBXO7-R498X mutation: phenotypic variability from chorea to early onset parkinsonism within a family.
abstract: OBJECTIVE
  FBXO7 mutations (PARK 15), first reported in 2008, are among the monogenic causes of early-onset parkinsonism. Classically, PARK 15 was suggested to correspond to previously described pallido-pyramidal syndrome. Here, we report clinical and genetic findings in a unique family of Kurdish origin with an FBXO7 mutation and presenting with diverse clinical phenotypes.
  
  
  METHODS
  The family consisted of 14 members (12 offspring) of whom three were affected. Two of these three siblings were examined in our clinic. DNA samples from the index case and his elder sister were subjected to homozygosity mapping and exomic sequencing.
  
  
  RESULTS
  The index case had progressive speech problems, severe apathy, chorea, and tics at presentation and developed very mild parkinsonism and postural instability after 3 years. His sister had young-onset asymmetric tremor-dominant parkinsonism with some atypical features, such as early development of postural instability, tics, and tachyphemic speech. She died of an akinetic-rigid condition and had not developed chorea. A homozygous R498X mutation was found in both patients (NM_012179; chr22:31,224,440). This result was further confirmed by Sanger sequencing in both patients, their consanguineous parents, and their maternal grandfather; the latter three were found to be heterozygous for the mutation (c.C1492T; p.R498X).
  
  
  CONCLUSIONS
  The family presented here broadens the clinical spectrum of parkinsonism to include tics and chorea, in addition to the parkinsonian-pyramidal phenotype, in connection with FBXO7 mutations and points to an intrafamilial phenotypic variation.
authors.affiliation: İstanbul University, Cerrahpaşa School of Medicine, Department of Neurology, 34098, K.M.Paşa, Istanbul, Turkey. Electronic address: draysegulgunduz@yahoo.com.
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Gündüz
authors.affiliation: Boğaziçi University, Department of Molecular Biology and Genetics, Neurodegeneration Research Laboratory, Istanbul, Turkey.
authors.forename: Aslı Gündoğdu
authors.initials: AG
authors.lastname: Eken
authors.affiliation: İstanbul University, İstanbul School of Medicine, Department of Neurology, Istanbul, Turkey.
authors.forename: Başar
authors.initials: B
authors.lastname: Bilgiç
authors.affiliation: İstanbul University, İstanbul School of Medicine, Department of Neurology, Istanbul, Turkey.
authors.forename: Hasmet A
authors.initials: HA
authors.lastname: Hanagasi
authors.affiliation: Yale University, Medical School, Neurogenetics Department, New Haven, CT, USA.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilgüvar
authors.affiliation: Yale University, Medical School, Neurogenetics Department, New Haven, CT, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Günel
authors.affiliation: Boğaziçi University, Department of Molecular Biology and Genetics, Neurodegeneration Research Laboratory, Istanbul, Turkey.
authors.forename: A Nazlı
authors.initials: AN
authors.lastname: Başak
authors.affiliation: İstanbul University, Cerrahpaşa School of Medicine, Department of Neurology, 34098, K.M.Paşa, Istanbul, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Ertan
mesh_terms: D000293:Adolescent; D002819:Chorea / Q000175:diagnosis / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D044783:F-Box Proteins; C489149:FBXO7 protein, human
keywords: Chorea; FBXO7 mutation; PARK-15; Pallido-pyramidal syndrome; Tic