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GENATLAS PHENOTYPE
last update : 16-06-2010
Symbol NPC2
Location 14q24.3
Name Niemann-Pick disease, type C2
Corresponding gene NPC2
Main clinical features
  • characterized by progressive deterioration of the central nervous system, hepatosplenomegaly and premature death
  • associated with lysosomal accumulation of LDL-derived cholesterol
  • in any cases, recurrent bronchitis and bronchiolitis with respiratory failure with increasing pulmonary fibrosis
  • mutation resulting in accumulation of unesterified cholesterol in late endosomes and lysosomes (PMID: 22179027))
    • Genetic determination autosomal recessive
    Prevalence 5p 100 of NPC cases
    Function/system disorder metabolism/lipoprotein-lipid
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function misfolded mutant protein retained in in the ER, recurrent mutation E20X highly
    missense   abnormal protein/loss of function located in the cholesterol-binding Evolutionarily Constrained Regions D domain, resulting in reduced amounts of a protein capable to reach the lysosome, but unable to efficiently bind cholesterol
    Remark(s)
    Genotype/Phenotype correlations . including milder forms with late onset and a prolonged course in patients with a splice mutation (IVS2 + 5G->A)
  • NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa associated to typical signs of pulmonary alveolar proteinosis with an abnormal intraalveolar accumulation of surfactant as well as macrophages (Aldana 2010)