title: Identification of a novel mutation in the spastin gene (SPG4) in an Italian family with hereditary spastic paresis.
abstract: Hereditary spastic paraparesis (HSP) includes a heterogeneous group of neurodegenerative diseases characterised by progressive spasticity and hyper-reflexia of the lower limbs. Autosomal dominant HSP type 4 is the most common clinical form, accounting for about 40-50% of autosomal dominant HSP families. This form is due to mutation of the gene encoding spastin (SPG4), an ATP-ase associated with a variety of cellular function (AAA). Here we describe a novel missense mutation (1297T>C; 391L>P) in exon 8 of SPG4 gene, identified in 2 members (mother and son) of an Italian family with autosomal dominant HSP, clinically pure in the mother and complicated in the son. The mutation lies in a highly conserved AAA box domain between amino acids 342 and 599 in spastin sequence. In both patients, this novel mutation was associated with the absence of relatively common clinical characteristics, such as vibratory sensory deficit and loss of sphincter control, and partial temporal epilepsy, particularly in the son, with infantile onset, secondarily generalised and moderately severe neuropsychiatric symptoms.
authors.affiliation: Mauro Baschirotto Institute for Rare Diseases, BIRD Foundation Onlus, Costozza (VI), Italy. matteo.bertelli@birdfoundation.org
authors.forename: M
authors.initials: M
authors.lastname: Bertelli
authors.forename: S
authors.initials: S
authors.lastname: Cecchin
authors.forename: L
authors.initials: L
authors.lastname: Lorusso
authors.forename: V
authors.initials: V
authors.lastname: Sidoti
authors.forename: A
authors.initials: A
authors.lastname: Fabbri
authors.forename: C
authors.initials: C
authors.lastname: Lapucci
authors.forename: A
authors.initials: A
authors.lastname: Buda
authors.forename: M
authors.initials: M
authors.lastname: Pandolfo
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D003596:Cytosine; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007558:Italy; D007930:Leucine; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D011392:Proline; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*; D000074181:Spastin; D013941:Thymine
chemical_list: D003596:Cytosine; D011392:Proline; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human; D007930:Leucine; D013941:Thymine