title: Characterisation of two deletions involving NPC1 and flanking genes in Niemann-Pick type C disease patients.
abstract: 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.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rodríguez-Pascau
authors.forename: Claudio
authors.initials: C
authors.lastname: Toma
authors.forename: Judit
authors.initials: J
authors.lastname: Macías-Vidal
authors.forename: Mónica
authors.initials: M
authors.lastname: Cozar
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.forename: Lilia
authors.initials: L
authors.lastname: Lykopoulou
authors.forename: Maria Josep
authors.initials: MJ
authors.lastname: Coll
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Vilageliu
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D005091:Exons; D017809:Fatal Outcome; D023061:Gene Order; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein