Wakil Salma M, Murad Hatem N, Baz Batoul M, Hagos Samiya T, Al-Amr Rana A, Al-Yamani Suad A, Al-Wadaee Salem M, Meyer Brian F, Bohlega Saeed A
Departments of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Neurosciences (Riyadh). 2012 Jan;17(1):48-52.
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.
评估与伴有胼胝体变薄（TCC）的常染色体隐性遗传性痉挛性截瘫（ARHSP）相关的spatacsin的突变情况和临床谱。
2008年2月至2011年3月在沙特阿拉伯利雅得的法赫德国王专科医院和研究中心进行了一项回顾性研究。对4个患有ARHSP-TCC的沙特阿拉伯无关家庭进行了研究，共有13名受影响个体。临床表现包括不同年龄（2至18岁）的步态障碍、伴有轻度至中度认知障碍的痉挛性截瘫以及2个家庭中有周围神经病变的证据。脑部MRI显示胼胝体变薄并伴有脑室周围白质改变和皮质萎缩。
全基因组扫描显示与SPG11基因座连锁。测序发现了4种突变。第一种是插入/缺失（indel），由3个碱基对（bp）的缺失和23 bp的插入组成（L1268L fsX），第二种是1个bp的缺失（S1923R fsX），第三种和第四种是无义突变（Q341X和R651X）。所有突变均预测spatacsin蛋白会过早截断。
我们报告了该基因中的2种新突变，包括一个比迄今鉴定出的任何其他突变都大得多的插入/缺失。这些突变的鉴定进一步证实了这些家庭中SPG11与ARHSP-TCC之间的因果关系。
