Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with thin corpus callosum.
Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with thin corpus callosum.
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DOI：
10.1016/j.parkreldis.2013.11.004
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发表时间：
2014-02
影响因子：
4.1
通讯作者：
Jing Ma;Likuan Xiong;Y. Chang;X. Jing;Weijun Huang;Bin Hu;Xinchong Shi;Weiping Xu;Yiming Wang;Xunhua Li
中科院分区：
文献类型：
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作者：
Jing Ma;Likuan Xiong;Y. Chang;X. Jing;Weijun Huang;Bin Hu;Xinchong Shi;Weiping Xu;Yiming Wang;Xunhua Li
遗传性痉挛截瘫(HSP)是一种在遗传和临床上都具有很强异质性的疾病。到目前为止，大约有52个位点和31个基因被报道与HSP的因果关系有关。该病的遗传方式可以是常染色体显性遗传、常染色体隐性遗传或X连锁隐性遗传。常染色体隐性遗传性HSP伴瘦痂(ARHSP-TCC)是该病的一种形式，隐性基因SPG11与41-77%的ARHSP-TCC病例有关，SPG11编码SPATACSIN蛋白，该蛋白在小脑中最显著表达。然而，人们对其功能知之甚少。尽管临床表现多种多样，但弥漫性小脑代谢低下尚未见报道。我们已经发现了一位HSP-TCC患者，其表现为明显的智能障碍而不是痉挛。18FDG-PET/CT检查显示双侧小脑弥漫性低代谢。应用Sanger测序对SPG11基因进行突变筛查，在患者中发现了新的复合杂合突变c.[5121_5122insAG]+[6859C>；T](p.[I1708RfsX2]+[Q2287X])。母亲携带C.5121_5122insAG突变，导致移码，预计会截短C末端的735个氨基酸；父亲携带C.6859C>；T突变，终止C末端的157个氨基酸。因此，这些突变可能导致野生型SPATACSIN功能的丧失。我们的结果提示SPATACSIN可能参与了小脑的代谢，新的突变为该基因的突变谱提供了更多的数据，这将有助于开发快速、准确的遗传诊断工具。
Hereditary spastic paraplegia (HSP) is a very heterogeneous disease, both genetically and clinically. To date, approximately 52 loci and 31 genes have been reported to be involved in the causality of HSP. The pattern of inheritance of the disease can be autosomal dominant, autosomal recessive, or X-linked recessive. Autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) is one form of this disease, and a recessive gene, SPG11, is responsible for 41–77% of all ARHSP-TCC cases.SPG11encodes the protein SPATACSIN, which is most prominently expressed in the cerebellum. However, little is known about its function. Despite diverse clinical presentations, diffuse hypometabolism in the cerebellum has not been reported previously. We have identified an HSP-TCC patient that presented with prominent intellectual disability rather than spasticity.18Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) examination showed diffuse hypometabolism in both cerebella. Mutation screening of theSPG11gene using Sanger sequencing identified the novel compound heterozygous mutation c.[5121_5122insAG]+[6859C>T] (p.[I1708RfsX2]+[Q2287X]) in the patient. The mother bears the c.5121_5122insAG mutation, which results in a frameshift and is predicted to truncate the 735 amino acids from the C-terminus, and the father carries the c.6859C>T mutation, which terminates the 157 amino acids from the C-terminus. Therefore, these mutations may result in the loss of function of wild-type SPATACSIN. Our results suggest that SPATACSIN may be involved in cerebella metabolism, and the novel mutations provide more data for the mutational spectrum of this gene, which will aid in the development of quick and accurate genetic diagnostic tools for this disease.