Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C
Journal
Journal of Neurology, Neurosurgery and Psychiatry
Journal Volume
76
Journal Issue
4
Pages
592-595
Date Issued
2005
Author(s)
Abstract
In patients with Niemann-Pick disease type C (NPC), an autosomal recessive lipid storage disorder, neurodegeneration can occur in early life. Vertical ophthalmoplegia and extrapyramidal signs may be seen. Cholestatic jaundice and hepatosplenomegaly occur frequently in patients with early onset disease, with bone marrow biopsies showing diffuse infiltration of foamy histiocytes. Cholesterol esterification in skin fibroblasts is reduced, resulting in intracellular accumulation of cholesterol. NPC1 mutations are responsible for the disease in ?95% of patients. NPC1 encodes a 1278 amino acid protein which contains 13 transmembrane domains. Over 130 mutations have been identified in NPC1, with over a third present within an NPC1 specific cysteine-rich domain positioned in a large extracellular loop. It has been proposed that the defect in cholesterol homoeostasis is the cause of neuronal apoptosis, but the precise role of the NPC1 protein and the functional implications of its mutations remain unknown. Although NPC is routinely diagnosed by biochemical analysis, identification of molecular defects helps confirm the diagnosis and enables family studies, and rapid, accurate prenatal diagnosis. This report describe the analysis of the NPC1 gene in five Taiwanese/Chinese patients with NPC. Six novel NPC1 mutations (N968S, G1015V, G1034R, V1212L, S738Stop, and 1635fs) were identified of which three are missense mutations located in the cysteine-rich domain. These are the first NPC1 mutations reported from Chinese patients with NPC.
SDGs
Other Subjects
DNA; adolescent; adult; article; autosomal recessive disorder; child; Chinese; clinical article; degenerative disease; denaturing high performance liquid chromatography; female; gene; gene mutation; human; lipidosis; male; neurologic disease; Niemann Pick disease; NPC1 gene; nuclear magnetic resonance imaging; onset age; polymerase chain reaction; priority journal; Adult; Apoptosis; Asian Continental Ancestry Group; Biopsy, Needle; Bone Marrow; Brain; Carrier Proteins; Child; Child, Preschool; China; Chromosomes, Human, Pair 18; DNA Mutational Analysis; Exons; Female; Humans; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Mutation, Missense; Neurons; Niemann-Pick Diseases; Point Mutation; Polymerase Chain Reaction; Taiwan
Type
journal article