title: The first Italian family with evidence of pyramidal impairment as phenotypic manifestation of Silver syndrome BSCL2 gene mutation.
abstract: Silver syndrome (SPG17) is a rare form of hereditary spastic paraparesis. Its relationship to distal hereditary motor neuropathy (dHMN) type V is underlined by the recent discovery of causative mutation in BSCL2 gene coding for a protein termed seipin, an integral membrane protein of endoplasmic reticulum, with unknown function. Here we report the third Italian family with dHMN and SPG17 in which two affected members harbor the heterozygous N88S mutation in the BSCL2 gene. The proband developed a severe paraparetic spastic gait, while, in the other Italian families reported so far, no signs of upper motor neuron involvement were observed. This family confirms the clinical heterogeneity associated with this specific mutation. Moreover, this is the first report in which neuroimaging seems to confirm the pyramidal alterations in dHMN associated to SPG17.
authors.affiliation: Department of Neuroscience O U of Neurology, S Chiara Hospital, University of Pisa, Pisa, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Cafforio
authors.forename: Rosanna
authors.initials: R
authors.lastname: Calabrese
authors.forename: Nicola
authors.initials: N
authors.lastname: Morelli
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Selina
authors.initials: S
authors.lastname: Piazza
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinuzzi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
authors.forename: Francesco
authors.initials: F
authors.lastname: Crippa
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D010525:Peripheral Nerves / Q000503:physiopathology; D010641:Phenotype; D011712:Pyramidal Tracts / Q000503:physiopathology*; D035583:Rare Diseases; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D005819:Genetic Markers