Autosomal recessive hereditary spastic paraplegia with thin corpus callosum among Saudis

To assess the mutational and clinical spectrum of spatacsin associated with autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC).

A retrospective study was carried out at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from February 2008 until March 2011. Four unrelated Saudi Arabian families with ARHSP-TCC were studied, totaling 13 affected individuals. Clinical presentations included gait disturbance at variable ages (2-18 years), spastic paraplegia with mild to moderate cognitive impairment and evidence of peripheral neuropathy in 2 families. Brain MRI showed TCC accompanied by periventricular white matter changes and cortical atrophy.

A genome wide scan demonstrated linkage to the SPG11 locus. Sequencing revealed 4 mutations. The first is an insertion/deletion (indel) consisting of a 3 base pair (bp) deletion and 23 bp insertion (L1268L fsX), the second is a one bp deletion (S1923R fsX), and the third and the fourth are nonsense mutations (Q341X and R651X). All mutations predict premature truncation of the spatacsin protein.

We report 2 novel mutations in this gene, including an indel considerably larger than any other identified to date. The identification of these mutations further confirms the causative link between SPG11 and ARHSP-TCC in these families.