English abstract
Hereditary Spastic Paraplegia (HSP) is a descriptive diagnosis of a phenotypically and genetically diverse group of disorders. Researchers have reported autosomal dominant, autosomal recessive, and X-linked recessive mode of inheritance. So far 29 loci have been mapped and 11 genes identified in different chromos clinically classified as two forms, the pure (uncomplicated) and the complicated form which involves other neurodegenerative symptoms. In a recent study, two consanguineous Omani families (A and B) were characterized clinically and radiologically with complicated autosomal recessive HSP. The affected individuals in family A had in addition to spastic paraplegia thin corpus callosum and mental retardation, whereas in family B two of three affected individuals had epilepsy. A genome wide scan and linkage analysis in both families identified a locus on chromosome 8p12-p11.21. This locus spans 9 CM, between markers D8S1820 and D85532 with the highest combined lod score of 7,077 at marker D8S505, Among the 30 genes located in this region Neuregulin-1 and KF13B are interesting functional candidate genes for HSP. KIF13B gene shares a kinesin motor domain with KIF5A gene located on chromosome 12. Two studies have reported mutations in the kinesis motor domain of KIF5A in two families with autosomal dominant HSP (SPG10). In this study 4 samples from each family (father, mother, affected and unaffected) were screened by sequencing for disease causing mutation in 38 known exons of KIF13B gene. Three SNPs segregating with disease locus in family B were detected, further confirming the genetic locus. In addition, a new SNP in the intronic region at position (115179: A/G) of the gene was detected in family B. This family was found to have more SNPs than family A suggesting a distant genetic relationship. Using RFLP all SNPs were found in 20 random Omani samples. Although no disease causing mutation was found in KIF13B, this gene cannot be excluded as a candidate gene for HSP in these families. Two more exons were added to this gene since this project was started and therefore annotation of this gene may not yet be completed. In addition to the exonic regions, promoter and other regulatory elements need to be sequenced before a final conclusion can be made in the involvement of KIF13B in HSP
