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Mariangela Lo Giudice, BS; Marcella Neri, MD; Michele Falco, BS; Maurizio Sturnio, BS; Elisa Calzolari, MD; Daniela Di Benedetto, PhD; Marco Fichera, PhD

Arch Neurol. 2006;63:284-287.

Background  To our knowledge, up to now, only 2 mutations in the KIF5A gene, a member of the kinesin superfamily, have been identified as the molecular cause of early-onset autosomal dominant hereditary spastic paraparesis (ADHSP).

Objective  To assess the genetic defect in a family with late-onset ADHSP.

Patients and Methods  Only the proband agreed to undergo complete neurological testing and mutational analysis. The proband was screened for mutations in the spastin, atlastin, NIPA1, and KIF5A genes, either by denaturing high-performance liquid chromatography or sequence analysis.

Results  The history of the family was consistent with ADHSP characterized by late onset of the disease. Mutational analysis results were negative for the spastin, atlastin, and NIPA1 genes but identified a missense mutation (c.1082C>T) in the coiled-coil coding region of the KIF5A gene.

Conclusions  This finding enlarges the phenotypic spectrum of ADHSP linked to KIF5A and enhances the role of that gene in the epidemiology of this disease. We propose that the KIF5A gene should be routinely analyzed in patients with hereditary spastic paraplegia negative for spastin and atlastin mutations.

Author Affiliations: Genetic Diagnostic Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Oasi Maria SS, Troina, Italy (Mss Lo Giudice and Falco, Mr Sturnio, and Drs Di Benedetto and Fichera); Department of Experimental Medicine and Diagnostics, Medical Genetics Service, University of Ferrara, Ferrara, Italy (Drs Neri and Calzolari).

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