Dataset Information

Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test.

ABSTRACT: Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of NPC1 gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying distinct sequence variants. Filipin staining was used to test for complementation of the phenotype. The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and 24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met, and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance. Moreover, we present a system that can be utilized to screen for new drugs.

SUBMITTER: Feng X

PROVIDER: S-EPMC6834306 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test.

Feng Xiao X Cozma Claudia C Pantoom Supansa S Hund Christina C Iwanov Katharina K Petters Janine J Völkner Christin C Bauer Claudia C Vogel Florian F Bauer Peter P Weiss Frank U FU Lerch Markus M MM Knospe Anne-Marie AM Hermann Andreas A Frech Moritz J MJ Luo Jiankai J Rolfs Arndt A Lukas Jan J

International journal of molecular sciences 20191019 20

Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of NPC1 ...[more]

PMID: 31635081

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Dataset Information

Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test.

Publications

Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test.

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