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Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2

Klünemann, Hans H ; Elleder, Milan ; Kaminski, Wolfgang E ; Snow, Karen ; Peyser, Janis M ; O'Brien, John F ; Munoz, David ; Schmitz, Gerd ; Klein, Helmfried E ; Pendlebury, William W

Annals of neurology, 2002-12, Vol.52 (6), p.743-749 [Peer Reviewed Journal]

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  • Title:
    Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2
  • Author: Klünemann, Hans H ; Elleder, Milan ; Kaminski, Wolfgang E ; Snow, Karen ; Peyser, Janis M ; O'Brien, John F ; Munoz, David ; Schmitz, Gerd ; Klein, Helmfried E ; Pendlebury, William W
  • Subjects: Glycoproteins - genetics ; Pedigree ; Humans ; Atrophy - genetics ; Adult ; Female ; Male ; Mutation - genetics ; Niemann-Pick Diseases - pathology ; Niemann-Pick Diseases - genetics ; Frontal Lobe - pathology ; Carrier Proteins ; Index Medicus
  • Is Part Of: Annals of neurology, 2002-12, Vol.52 (6), p.743-749
  • Description: This is the first description of slowly progressive Niemann–Pick disease type C (NPC) without the typical lysosomal storage in bone marrow and viscera in two descendants of a group of 17th century French‐Canadians. The index patient was a married 43‐year‐old woman with onset of dementia in her thirties, later followed by the development of ataxia and athetoid movements. Her autopsy disclosed frontal lobe atrophy, neurolysosomal storage with oligolamellar inclusion and tau‐positive neurofibrillary tangles. Of the 119 family members screened, only a married 42‐year‐old sister displayed symptoms of a dementia. Both women displayed vertical supranuclear ophthalmoplegia; expressive aphasia; concrete, stimulus‐bound, perseverative behavior; and impaired conceptualization and planning. Cultured fibroblasts showed decreased cholesterol esterification and positive filipin staining, but no mutation was detected in coding or promoter regions of the NPC1 gene using conformation sensitive gel electrophoresis and sequencing. Sequencing showed a homozygous gene mutation that is predicted to result in an amino acid substitution, V39M, in the cholesterol binding protein HE1 (NPC2). Adult‐onset NPC2 with lysosomal storage virtually restricted to neurons represents a novel phenotypic and genotypic variant with diffuse cognitive impairment and focal frontal involvement described for the first time. Ann Neurol 2002;52:000–000
  • Publisher: New York: Wiley Subscription Services, Inc., A Wiley Company
  • Language: English
  • Identifier: ISSN: 0364-5134
    EISSN: 1531-8249
    DOI: 10.1002/ana.10366
    PMID: 12447927
  • Source: © ProQuest LLC All rights reserved

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