title: Novel DYT11 gene mutation in patients without dopaminergic deficit (SWEDD) screened for dystonia.
abstract: OBJECTIVE
  To test the hypothesis that adult-onset primary dystonia may be the underlying etiology of tremulous patients with clinical diagnosis of Parkinson disease (PD) but without evidence of dopaminergic deficit at nigrostriatal SPECT imaging.
  
  
  METHODS
  We retrospectively reviewed clinical and imaging data of patients with clinical diagnosis of PD assessed at our tertiary movement disorder clinic, who underwent dopamine transporter SPECT imaging consecutively between 2002 and 2011. Molecular screening for DYT1, DYT5, DYT6, DYT11, and DYT16 dystonia genes was performed in all cases who met the following criteria at the time of SPECT scan: (1) clinical diagnosis of PD; (2) normal dopamine transporter SPECT; (3) asymmetric rest tremor, with or without postural/kinetic component; (4) ≥ 12-month follow-up; and (5) normal brain MRI. We excluded subjects with (6) overt dystonic features, and (7) head or voice tremor.
  
  
  RESULTS
  Twenty-three subjects were eligible for molecular analysis. Positive family history for tremor or PD was present in 45% of probands. We found one patient with a novel heterozygous frameshift mutation in the DYT11 gene (c.1058-1062 delCACCA/p.Gln352fsX376). Electrophysiologic study of tremor revealed that the main contributor was 5- to 6-Hz pseudo-rhythmic myoclonus, primarily involving extensor muscles. In 2 brothers, we found a missense variant in the DYT5 gene (c.334A>G; p.Thr112Ala) of uncertain pathogenicity in humans.
  
  
  CONCLUSIONS
  Our findings provide further support to the hypothesis that adult-onset monogenic dystonia may underlie a "PD look-alike" clinical phenotype. In addition to dystonic tremor, pseudo-rhythmic myoclonus may be mischaracterized as "rest tremor."
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. roberto.cilia@gmail.com.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cilia
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Reale
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Castagna
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nasca
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Muzi-Falconi
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Barzaghi
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marzegan
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Granata
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marotta
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sacilotto
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vallauri
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.affiliation: From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
mesh_terms: D000328:Adult; D000368:Aged; D020821:Dystonic Disorders / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics; D012189:Retrospective Studies; D049031:Sarcoglycans / Q000235:genetics*
chemical_list: D049031:Sarcoglycans