cqvip:Background: Mutations in a novel GTPase gene SPG3A cause an autosomal dominant hereditary spastic paraplegia linked to chromosome 14q (SPG3), which accounts f or approximately 10%to 15%of all autosomal dominant hereditary spastic paraple gia cases. The mutational spectrum of the SPG3A gene and the phenotype/genotype correlations have not yet been established. Objective: To describe a kindred wit h an infantile onset of hereditary spastic paraplegia caused by a novel mutation in the SPG3A gene. Patients: Complete neurological examination and genetic anal ysis were performed on 6 affected members of a small African American kindred. L inkage analysis to genetic markers near autosomal dominant hereditary spastic pa raplegia loci on chromosomes 2p and 14q was performed. The coding sequence of th e SPG3A gene was analyzed, and the identified change in the sequence was tested for being a benign polymorphism by sequencing 200 chromosomes from normal contro ls. Results: Every affected individual had signs of uncomplicated spastic parapa resis without additional neurological abnormalities. None of the affected family members had ever walked normally. The history was consistent with an infantile onset, despite the normal acquisition of motor milestones. Genetic analysis sugg ested linkage to the SPG3A locus on chromosome 14q. Analysis of the SPG3A gene r evealed a missense mutation C635T, predicted to result in a threonine to isoleuc ine substitution at codon 156. Analysis of 200 normal chromosomes did not identi fy the same change in healthy subjects. Conclusion: We report a novel muta tion in the SPG3A gene in an African American family with an infantile onset of auto somal dominant hereditary spastic paraplegia.
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