SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia.

Abstract

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common form of complex hereditary spastic paraplegia. The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and given the designation SPG11. Recently, the gene encoding spatacsin (KIAA1840) has been shown to contain mutations that underlie the majority of ARHSP-TCC cases. We present a complete analysis of the 40 coding exons of this gene in patients with sporadic (n = 25) or familial (20 probands) complex hereditary spastic paraplegia with and without thinning of the corpus callosum. We identified seven mutations, including deletions, insertions, and nonsense mutations, which were all predicted to lead to premature truncation of the protein. We conclude that mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia but an infrequent cause of sporadic complex hereditary spastic paraplegia.