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@ARTICLE{Schneider:141620,
      author       = {Schneider, Susanne A and Tahirovic, Sabina and Hardy, John
                      and Strupp, Michael and Bremova-Ertl, Tatiana},
      title        = {{D}o heterozygous mutations of {N}iemann-{P}ick type {C}
                      predispose to late-onset neurodegeneration: a review of the
                      literature.},
      journal      = {Journal of neurology},
      volume       = {268},
      number       = {6},
      issn         = {0340-5354},
      address      = {Berlin},
      publisher    = {Springer77118},
      reportid     = {DZNE-2020-07944},
      pages        = {2055-2064},
      year         = {2021},
      abstract     = {Monogenic diseases are important models for the study of
                      neurodegenerative diseases, such as Parkinson's disease (PD)
                      and dementia. Notably, for some disorders, homozygosity is
                      associated with a complex metabolic disease, while
                      heterozygosity predisposes to late-onset neurodegeneration.
                      For instance, biallelic glucocerebrosidase gene mutations
                      cause Gaucher's disease, while heterozygous mutations are a
                      common genetic risk factor for late-onset PD. Little is
                      known about similar risks of related diseases, such as
                      Niemann-Pick type C (NPC). Given that both conditions map
                      into related, i.e., lysosomal, pathways, we hypothesize a
                      similar risk of single-NPC gene mutations. Indeed, there is
                      increasing evidence based on clinical observations in humans
                      and animal studies. Here we review the current knowledge of
                      NPC heterozygosity.Family history studies suggest a high
                      proportion of late-onset neurodegenerative diseases in NPC
                      families. We identified 19 cases with heterozygous NPC
                      mutations in the literature who presented with a
                      neurodegenerative disease, including levodopa-responsive PD,
                      atypical parkinsonism (PSP, CBD), dystonia or dementia with
                      a mean age at onset of about 57 years (range 8-87).
                      Consistent splenomegaly and mildly abnormal filipin staining
                      results have also been reported in heterozygous gene
                      mutation carriers. Imaging and pathological data support
                      this notion.This finding has wider implications in so far as
                      NPC-related forms of Parkinsonian syndromes, dementia, motor
                      neuron disease and other neurodegenerative disorders may
                      benefit from NPC-mechanistic therapies, in particular
                      related to lysosomal dysfunction. Further research is
                      warranted to generate systematic data of heterozygous
                      mutation carriers, including longitudinal data.},
      subtyp        = {Review Article},
      keywords     = {Adolescent / Adult / Aged / Aged, 80 and over / Animals /
                      Child / Gaucher Disease / Glucosylceramidase: genetics /
                      Heterozygote / Humans / Middle Aged / Mutation /
                      Neurodegenerative Diseases: genetics / Niemann-Pick Disease,
                      Type C: genetics / Young Adult},
      cin          = {Pre 2020 / AG Tahirovic},
      ddc          = {610},
      cid          = {I:(DE-2719)999999 / I:(DE-2719)1140003},
      pnm          = {899H - Addenda (POF3-899H) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF3-899H / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31701332},
      doi          = {10.1007/s00415-019-09621-5},
      url          = {https://pub.dzne.de/record/141620},
}