PT  - JOURNAL ARTICLE
AU  - Wakil, Salma M.
AU  - Murad, Hatem N.
AU  - Baz, Batoul M.
AU  - Hagos, Samiya T.
AU  - Al-Amr, Rana A.
AU  - Al-Yamani, Suad A.
AU  - Al-Wadaee, Salem M.
AU  - Meyer, Brian F.
AU  - Bohlega, Saeed A.
TI  - Autosomal recessive hereditary spastic paraplegia with thin corpus callosum among Saudis
DP  - 2012 Jan 01
TA  - Neurosciences Journal
PG  - 48--52
VI  - 17
IP  - 1
4099  - http://nsj.org.sa/content/17/1/48.short
4100  - http://nsj.org.sa/content/17/1/48.full
SO  - Neurosciences (Riyadh)2012 Jan 01; 17
AB  - OBJECTIVE: To assess the mutational and clinical spectrum of spatacsin associated with autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC).METHODS: 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.RESULTS: 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.CONCLUSION: 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.