Journal
EUROPEAN JOURNAL OF NEUROLOGY
Volume 15, Issue 10, Pages 1065-1070Publisher
WILEY
DOI: 10.1111/j.1468-1331.2008.02247.x
Keywords
heredity spastic paraplegia; KIAA1840; Spatacsin; SPG11
Categories
Funding
- Medical Research Council
- National Institute on Aging
- National Institutes of Health
- Department of Health and Human Services, MD, USA
- Department of Health's NIHR Biomedical Research Centres
- MRC [G108/638] Funding Source: UKRI
- Medical Research Council [G108/638] Funding Source: researchfish
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Background: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum is a distinct and usually severe form of complex hereditary spastic paraplegia classified as SPG11. Recently mutations on SPG11 gene (KIAA1840), which is localized to chromosome 15q13-q15, were shown to cause the majority of SPG11 cases. Methods: We analysed the 40 coding exons of this gene in the probands from eight families with complex ARHSP, four of these families had a thin corpus callosum and two has mild thinning. Results: Three families were identified with novel mutations in the SPG11 gene. One family was of Asian origin with a homozygous nonsense mutation and had a very severe phenotype but only very mild thinning of the corpus callosum. In the other two English families the parents were unrelated and the mutations were compound heterozygotes. In these two families the phenotype was mild and both probands had a thin corpus callosum. Conclusions: Given the probable mechanism of action of the mutations in the Spatacsin gene, we discuss the probable genotype phenotype correlations in these families. This study confirms the frequent occurrence of Spatacsin mutations in complex ARHSP with genotype phenotype effects and exposes the spectrum of clinical heterogeneity in SPG11.
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