title: Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.
abstract: Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP.
authors.affiliation: Molecular Diagnostic Centre for Hereditary Diseases (CDGM), Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Gran Via 199, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: etoledano@idibell.cat.
authors.forename: Eva
authors.initials: E
authors.lastname: López
authors.affiliation: Neuromuscular Unit, Neurology Department, Hospital Universitari de Bellvitge, IDIBELL.C/Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Casasnovas
authors.affiliation: Molecular Diagnostic Centre for Hereditary Diseases (CDGM), Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Gran Via 199, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Giménez
authors.affiliation: Laboratorio Dr. Echevarne, C/Provença 312, 08037 Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Santamaría
authors.affiliation: Neurology Department, Hospital de Laredo, Avda. Derechos humanos s/n 39.770 Laredo, Cantabria, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Terrazas
authors.affiliation: Molecular Diagnostic Centre for Hereditary Diseases (CDGM), Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Gran Via 199, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Volpini
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology; D013030:Spain; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology
chemical_list: C500506:KIF5A protein, human; D016547:Kinesins
keywords: Intention tremor; KIF5A; Motor domain; Sensory neuropathy; Spastic paraplegia