title: Increased NPC1 mRNA in skin fibroblasts from Niemann-Pick disease type C patients.
abstract: Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid-storage disease that is characterized by progressive neurodegeneration and hepatosplenomegaly. Since identification of the NPC1 gene in 1997, a total of 120 disease-causing mutations have been reported. In this study, two novel mutations were identified, namely c.2508[-2509]A del (837Fs-838X) in exon 16 and T3194G (V1065G) in exon 21. To explore the impact of NPC1 mutations on transcription of this gene, we analyzed NPC1 mRNA levels in skin fibroblasts derived from NP-C patients. Fibroblasts from patients with missense mutations showed increased levels of NPC1 mRNA while fibroblasts from patients with a specific frameshift mutation showed mRNA levels similar to those of normal control subjects. These results suggest that NPC1 transcription levels are altered in cells with mutations in the NPC1 gene.
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan. nikau@basil.freemail.ne.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Feng
authors.forename: Katsumi
authors.initials: K
authors.lastname: Higaki
authors.forename: Miyako
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Haruaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohno
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D016368:Frameshift Mutation / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D012333:RNA, Messenger