Novel compound heterozygous mutation in NPC1 gene cause Niemann–Pick disease type C with juvenile onset

Maria Cristina Costanzo, Antonio Gennaro Nicotera, Mirella Vinci, Aurelio Vitello, Agata Fiumara, Francesco Calì, Sebastiano Antonino Musumeci

Research output: Contribution to journalArticlepeer-review


Niemann–Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in ~5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G > A (p.Arg518Gln), paternally inherited, and c.1270C > T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C > T (p.Pro424Ser) as a new causative mutation of NPC.

Original languageEnglish
Article number30
JournalJournal of Genetics
Issue number1
Publication statusPublished - Dec 1 2020


  • cognitive impairment
  • Miglustat
  • missense mutation
  • Niemann–Pick disease type C
  • NPC1 gene

ASJC Scopus subject areas

  • Genetics


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