title: New Niemann-Pick type C1 gene mutation associated with very severe disease course and marked early cerebellar vermis atrophy.
abstract: Niemann-Pick type C is an autosomal recessive lipid storage disease caused by mutations in the NPC1 or NPC2 gene. In childhood-onset Niemann-Pick type C, the usual course is slowly progressive, with normal cerebral magnetic resonance at onset. Here the authors present the case of a patient carrying 2 compound heterozygous NPC1 mutations: the known nonsense mutation (p.Trp833X) in exon 16 and a novel missense mutation (p.Ile609Phe) in exon 12. At onset, the patient presented ataxia, cognitive decline, and epilepsy, with early cerebral atrophy and marked cerebellar vermis atrophy. The course of the disease was rapid, and the patient died within 1-2 years of onset. A possible phenotype-genotype correlation is discussed. This case further expands the clinical spectrum and the genetic heterogeneity of Niemann-Pick type C due to NPC1 mutations.
authors.affiliation: 1Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fusco
authors.forename: Angelo
authors.initials: A
authors.lastname: Russo
authors.forename: Daniela
authors.initials: D
authors.lastname: Galla
authors.forename: Uros
authors.initials: U
authors.lastname: Hladnik
authors.forename: Daniele
authors.initials: D
authors.lastname: Frattini
authors.forename: Elvio Della
authors.initials: ED
authors.lastname: Giustina
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000473:pathology*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins
keywords: Niemann-Pick type C1; compound heterozygote; early cerebellar atrophy; severe course