title: A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia.
abstract: The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterised by lower limb spasticity and weakness. Mutations in NIPA1 (Nonimprinted in Prader-Willi/Angelman syndrome 1) have recently been identified as a cause of autosomal dominant pure HSP, with one mutation described in two unrelated families. NIPA1 has no known function but is predicted to possess nine transmembrane domains and may function as a receptor or transporter. Here we present a large British pedigree in which linkage analysis conclusively demonstrates linkage to the NIPA1 locus (maximum multipoint LOD score 4.6). Subsequent mutation analysis identified a novel missense substitution in a highly conserved NIPA1 residue (G106R) which further confirms a causative link between NIPA1 mutation and autosomal dominant hereditary spastic paraplegia.
authors.affiliation: Department of Medical Genetics, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE, UK.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Reed
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Wilkinson
authors.forename: Heema
authors.initials: H
authors.lastname: Patel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chatonnet
authors.forename: Dimitri
authors.initials: D
authors.lastname: Robay
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patton
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Crosby
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D006113:United Kingdom
chemical_list: D008565:Membrane Proteins; C478824:NIPA1 protein, human