Genomic structure and expression analysis of the spastic paraplegia gene, SPG7

SPG7 is a newly identified gene involved in an autosomal recessive form of hereditary spastic paraplegia (HSP), a genetically heterogeneous group of n eurodegenerative disorders. This gene encodes a protein characterized as a nuclear-encoded mitochondrial metalloprotease. The present report describes the genomic structure of the SPG7 gene. It is organized into 17 exons rang ing from 78 to 242 bp and spans approximately 52 kb within three overlappin g cosmids. The exon/intron boundaries and all splice junctions are consiste nt with the published consensus sequences for donor and acceptor sites. The provided genomic structure of SPG7 should facilitate the screening for mut ations in this gene in patients with HSP and other related mitochondrial di sease syndromes. SPG7 has been mapped to chromosome 16q24.3, a region of fr equent loss of heterozygosity (LOH) seen in sporadic breast and prostate ca ncer. We have performed single-strand conformation polymorphism analysis of ten exons of this gene in a number of sporadic breast cancer samples showi ng LOH at 16q24.3. No mutations were detected; only single nucleotide polym orphisms were observed in exon 11, intron 7, intron 10 and intron 12. An ex pression analysis study has revealed the differential expression of SPG7 mR NA in various tissues and at different developmental stages.