title: GRIN1 polymorphisms do not affect susceptibility or phenotype in NMDA receptor encephalitis.
abstract: OBJECTIVE
  To determine whether distinct single nucleotide polymorphisms (SNPs) within the glutamate receptor ionotropic NMDA 1 gene (GRIN1) are associated with NMDA receptor (NMDAR) encephalitis and whether these same variants are associated with variability in the clinical presentation and course of affected patients.
  
  
  METHODS
  We performed clinical follow-up on 48 patients with NMDAR encephalitis and NMDAR autoantibodies detected in serum or CSF. All RefSeq GRIN1 coding exons were sequenced in 39 Caucasian-European patients, and the frequencies of SNPs were compared with those of an ethnically similar population using a case-control study design. Predetermined clinical variables were compared between patients with and without identified SNPs.
  
  
  RESULTS
  Two SNPs were identified in GRIN1: 24 (62%) Caucasian-European patients with NMDAR encephalitis had alternate alleles at both rs6293 (exon 6) and rs1126442 (exon 7; exon numbering according to NM_001185090). The SNPs were in complete linkage disequilibrium. The frequency of these variants did not differ between patients with NMDAR encephalitis and ethnically matched individuals in the general population. No differences in clinical presentation, measures of disease severity, clinical course, or outcomes were observed between patients with different genotypes at these SNPs.
  
  
  CONCLUSIONS
  Disease susceptibility or course in patients with NMDAR encephalitis was not strongly affected by SNPs in GRIN1. This study provides an estimate of the frequency of SNPs in GRIN1 in patients with NMDAR encephalitis and emphasizes the need for multisite collaborative studies enrolling larger numbers of patients to identify the genetic contributions to NMDAR encephalitis.
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Day
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Benseler
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Paton
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.affiliation: Department of Medicine (G.S.D., D.M.A.), Division of Neurology, and Dalla Lana School of Public Health (A.D.P.), University of Toronto, Ontario, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, and German Center for Neurodegenerative Diseases (DZNE) (H.P.), Berlin, Germany; Department of Rheumatology, Alberta Children's Hospital, and Research Institute (S.M.B.), University of Calgary, Alberta, Canada; The Centre for Applied Genomics (T.A.P., A.D.P.), The Hospital for Sick Children, Toronto, Ontario, Canada; and University Health Network (D.M.A.), Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Andrade