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Regressive Autism Spectrum Disorder Expands the Phenotype of BSCL2/Seipin-Associated Neurodegeneration

  • Alice Poisson
    Correspondence
    Address correspondence to Alice Poisson, M.D., Ph.D., GénoPsy, CH le Vinatier, 69500, Bron, France.
    Affiliations
    GénoPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier and EDR-Psy Team (Centre National de la Recherche Scientifique & Lyon 1 Claude Bernard University), Lyon, France
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  • Nicolas Chatron
    Affiliations
    GENDEV, Centre de Recherche en Neurosciences de Lyon, UMR 529, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1028, Université Claude Bernard Lyon 1, Lyon, France

    HCL, Department of Genetics, Reference Center for Developmental Anomalies and Malformation Syndromes, Oullins, France
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  • Audrey Labalme
    Affiliations
    GENDEV, Centre de Recherche en Neurosciences de Lyon, UMR 529, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1028, Université Claude Bernard Lyon 1, Lyon, France

    HCL, Department of Genetics, Reference Center for Developmental Anomalies and Malformation Syndromes, Oullins, France
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  • Marianne Till
    Affiliations
    GENDEV, Centre de Recherche en Neurosciences de Lyon, UMR 529, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1028, Université Claude Bernard Lyon 1, Lyon, France

    HCL, Department of Genetics, Reference Center for Developmental Anomalies and Malformation Syndromes, Oullins, France
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  • Emmanuel Broussolle
    Affiliations
    UMR 5229, Centre National de la Recherche Scientifique, Institut des Sciences Cognitives Marc Jeannerod, Université de Lyon, Oullins, France

    Service de Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; and the Faculté de Médecine Lyon Sud Charles Mérieux, Université de Lyon, Oullins, France
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  • Damien Sanlaville
    Affiliations
    GENDEV, Centre de Recherche en Neurosciences de Lyon, UMR 529, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1028, Université Claude Bernard Lyon 1, Lyon, France

    HCL, Department of Genetics, Reference Center for Developmental Anomalies and Malformation Syndromes, Oullins, France
    Search for articles by this author
  • Caroline Demily
    Affiliations
    GénoPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier and EDR-Psy Team (Centre National de la Recherche Scientifique & Lyon 1 Claude Bernard University), Lyon, France
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  • Gaetan Lesca
    Affiliations
    GENDEV, Centre de Recherche en Neurosciences de Lyon, UMR 529, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1028, Université Claude Bernard Lyon 1, Lyon, France

    HCL, Department of Genetics, Reference Center for Developmental Anomalies and Malformation Syndromes, Oullins, France
    Search for articles by this author
      In 2013, Guillén-Navarro et al. (
      • Guillén-Navarro E.
      • Sánchez-Iglesias S.
      • Domingo-Jiménez R.
      • Victoria B.
      • Ruiz-Riquelme A.
      • Rábano A.
      • et al.
      A new seipin-associated neurodegenerative syndrome.
      ) described 6 Spanish patients from Murcia, Spain, affected with a lethal neurodegenerative syndrome during infancy. All the patients were homozygous or compound heterozygous for a rare BSCL2 exon 7–skipping variant. This disorder was called progressive encephalopathy with or without lipodystrophy, or Celia's encephalopathy (
      • Ruiz-Riquelme A.
      • Sánchez-Iglesias S.
      • Rábano A.
      • Guillén-Navarro E.
      • Domingo-Jiménez R.
      • Ramos A.
      • et al.
      Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease.
      ). Since then, no other case has been published, and the phenotypic variability of this genetic event remains unknown. Here, we report a female patient with regressive autism spectrum disorder (ASD) who developed atypical parkinsonism in adulthood. The patient carried two different potentially pathogenic variants that affected splicing of exon 7 in BSCL2.
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