Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia

In the current study, we report a novel mutation in a large Italian pedigree from southern Italy with autosomal dominant uncomplicated spastic paraplegia. We included 35 individuals from four generations. Significant linkage to the SPG3 locus on chromosome 14 was detected with a maximum LOD score of 4.58 at D14S255. Direct sequencing of the SPG3A gene revealed a G-->A mutation at position 818 in exon 7 of the gene. This mutation created an amino-acid change from Arg to Gln at codon 217. This is the first evidence of a mutation in the SPG3A gene that alters the RD motif of atlastin. These data also confirm that mutations in the SPG3A gene are causative of AD-HSP