title: RELN rare variants in myoclonus-dystonia.
abstract: BACKGROUND
  Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been established, indicating genetic heterogeneity.
  
  
  METHODS
  Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M-D syndrome, we performed homozygosity mapping combined with exome sequencing in a three-generation M-D family and genetically screened 24 additional patients with M-D.
  
  
  RESULTS
  We found co-segregation of the rare missense variant Thr1904Met in the RELN gene. By additional screening of an M-D cohort, we identified co-segregation of RELN variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic RELN mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 SGCE-negative M-D patients carried RELN rare missense variants.
  
  
  CONCLUSIONS
  We propose that RELN mutations contribute to the genetic heterogeneity of M-D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity.
authors: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Genome Analysis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Justus L
authors: JL
authors: Groen
authors: Katja
authors: K
authors: Ritz
authors: Hamid
authors: H
authors: Jalalzadeh
authors: Sandra M A
authors: SM
authors: van der Salm
authors: Aldo
authors: A
authors: Jongejan
authors: Olaf R
authors: OR
authors: Mook
authors: Martin A
authors: MA
authors: Haagmans
authors: Aeilko H
authors: AH
authors: Zwinderman
authors: Mahdi M
authors: MM
authors: Motazacker
authors: Raoul C
authors: RC
authors: Hennekam
authors: Frank
authors: F
authors: Baas
authors: Marina A J
authors: MA
authors: Tijssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D020821:Dystonic Disorders / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: RELN; genetics; myoclonus-dystonia