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© 2006 American Academy of Neurology A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsyFrom the College of Medicine and Health Sciences (S.A.-Y., H.A.-B., M.A.-K., P.C., R.K., P.C.J., R.A.B.), Sultan Qaboos University, Muscat, Oman; Faculty of Medicine and Health Sciences (L.I.A.-G., A.G., L.S.), UAE University, Al-Ain, United Arab Emirates; Department of Molecular Genetics (P.D., E.D., C.V.), Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium; and Laboratory of Statistical Genetics (A.P.), The Rockefeller University, New York, NY. Address correspondence and reprint requests to Dr. Al-Yahyaee Said Ali Suleiman, Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Al-Khoud 123, Sultanate of Oman; e-mail: syahyaee{at}squ.edu.om Background: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. Methods: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. Results: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. Conclusion: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.
Supported in part by grant IG/MED/01/03 from Sultan Qaboos University and the Molecular Genetics Fund of VIB8, University of Antwerp, Belgium. Disclosure: The authors report no conflicts of interest. Received June 2, 2005. Accepted in final form December 21, 2005.
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