Characterisation of two deletions involving NPC1 and flanking genes in Niemann-Pick type C disease patients

Mol Genet Metab. 2012 Dec;107(4):716-20. doi: 10.1016/j.ymgme.2012.10.004. Epub 2012 Oct 14.


Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal disorder characterised by the accumulation of a complex pattern of lipids in the lysosomal-late endosomal system. More than 300 disease-causing mutations have been identified so far in the NPC1 and NPC2 genes, including indel, missense, nonsense and splicing mutations. Only one genomic deletion, of more than 23 kb, has been previously reported. We describe two larger structural variants, encompassing NPC1 and flanking genes, as a cause of the disease. QMPSF, SNP inheritance and CytoScan® HD Array were used to confirm and further characterise the presence of hemizygous deletions in two patients. One of the patients (NPC-57) bore a previously described missense mutation (p.T1066N) and an inherited deletion that included NPC1, C18orf8 and part of ANKRD29 gene. The second patient (NPC-G1) had a 1-bp deletion (c.852delT; p.F284Lfs*26) and a deletion encompassing the promoter region and exons 1-10 of NPC1 and the adjacent ANKRD29 and LAMA3. This study characterised two novel chromosomal microdeletions at 18q11-q12 that cause NPC disease and provide insight into missing NPC1 mutant alleles.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Carrier Proteins / genetics*
  • Child, Preschool
  • Exons
  • Fatal Outcome
  • Gene Order
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Introns
  • Membrane Glycoproteins / genetics*
  • Niemann-Pick C1 Protein
  • Niemann-Pick Disease, Type C / diagnosis
  • Niemann-Pick Disease, Type C / genetics*
  • Pedigree
  • Sequence Deletion*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein