title: 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.
abstract: 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. SPG11 encodes 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. (18)Fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) examination showed diffuse hypometabolism in both cerebella. Mutation screening of the SPG11 gene 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.
authors: Central Laboratory, Bao'an Maternal and Children Health Hospital, Shenzhen 518133, China.
authors: Jing
authors: J
authors: Ma
authors: Central Laboratory, Bao'an Maternal and Children Health Hospital, Shenzhen 518133, China.
authors: Likuan
authors: L
authors: Xiong
authors: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Yu
authors: Y
authors: Chang
authors: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Xiangyi
authors: X
authors: Jing
authors: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Weijun
authors: W
authors: Huang
authors: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Bin
authors: B
authors: Hu
authors: Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Xinchong
authors: X
authors: Shi
authors: Department of Nuclear Medicine, Guangdong General Hospital, Guangzhou 510080, China.
authors: Weiping
authors: W
authors: Xu
authors: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: ywzhong@hotmail.com.
authors: Yiming
authors: Y
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: lxh59xyh@sina.com.
authors: Xunhua
authors: X
authors: Li
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D044466:Asian People; D001483:Base Sequence; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D064847:Multimodal Imaging; D009154:Mutation; D010375:Pedigree; D049268:Positron-Emission Tomography; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary; D014057:Tomography, X-Ray Computed
chemical_list: D011506:Proteins; C520412:SPG11 protein, human
keywords: Cerebella hypometabolism; Hereditary spastic paraplegia; Mutation; SPG11; Thin corpus callosum