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|LETTER TO EDITOR
|Year : 2022 | Volume
| Issue : 1 | Page : 424-426
Novel SPG11 Mutation in Hereditary Spastic Paraplegia with Thin Corpus Callosum
Shuang Li1, Lili Sun1, Guohua Zhao2, Xiaomin Liu1
1 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China
2 Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
|Date of Submission||08-Nov-2019|
|Date of Decision||02-Apr-2020|
|Date of Acceptance||26-Jul-2020|
|Date of Web Publication||28-Feb-2022|
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Jinan - 250014, Shandong
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Li S, Sun L, Zhao G, Liu X. Novel SPG11 Mutation in Hereditary Spastic Paraplegia with Thin Corpus Callosum. Neurol India 2022;70:424-6
Mutations in SPG11 are the major causes of autosomal recessive (AR) hereditary spastic paraplegia with thin corpus callosum (HSP-TCC). Herein, we report a novel SPG11 mutation in a Chinese HSP-TCC family [Figure 1]a.
|Figure 1: (a) Pedigree of the HSP-TCC family. The proband is indicated (arrow). The completely shaded symbol indicates a patient carrying the novel mutation. (b), (c) “Ears of the lynx” sign on axial brain MR images in the proband. The abnormal regions of the anterior forceps of the corpus callosum are indicated (arrows). (d-f) T1 sagittal image and DTI show a TCC. (g) Wild-type sequence. (h) The homozygous c.4744-1G. A mutation in the proband. (i) The heterozygous mutation in the parents and the brother. Black frames delineate the c.4744 nucleotide|
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A 12-year-old boy (II: 2, the proband) was admitted to the hospital due to tremor in the upper limbs, weakness, and spasticity in the lower limbs, and declined academic performance, which first appeared at about 8 years of age and slowly progressed. Cognitive dysfunction, cerebellar ataxia, lower limb spasticity, and bilateral Babinski signs were observed during the examination. His brain magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) revealed a TCC accompanied by periventricular white matter abnormal changes. The “ears of the lynx” sign was seen in the anterior forceps of the corpus callosum which appeared to be hyperintense on fluid-attenuated inversion recovery (FLAIR) and hypointense on T1 images [Figure 1]b,[Figure 1]c,[Figure 1]d,[Figure 1]e,[Figure 1]f. Therefore, this patient was considered to have HSP-TCC. The father (I: 1) and the mother (I: 2) were unrelated, and examinations of them and the brother (II: 1) were normal. All participants were of Han nationality from Shandong province, China. Informed consent was obtained. By whole-exome sequencing, we identified a novel homozygous mutation c. 4744-1G → A in SPG11 in the proband [Figure 1]h. The father, mother, and brother were heterozygous [Figure 1]i. The mutation was absent in 200 normal chromosomes.
HSP-TCC is characterized by progressive spastic paraparesis and cognitive impairment. In the present study, the proband presented cognitive impairment, cerebellar ataxia, and lower limb spasticity. A TCC was seen, and the “ears of the lynx” sign, which is highly specific for SPG11, was observed on his brain MR images, suggesting that brain MR is essential to diagnose HSP-TCC and helpful to differentiate HSP subtypes.,,, Mutation in SPG11 accounts for 21% of AR HSP cases. In our study, the novel mutation c. 4744-1G → A was identified at the conserved splice acceptor site of exon 28 of SPG11, suggesting a splice-site mutation. The mutation might cause skipping of exon 28 or activation of the potential acceptor splice site at c. 4752-4753AG. A concomitant frameshift may occur and encode a truncated and dysfunctional spatacsin protein. In 2020, another frameshift deletion mutation c. 4746delT in exon 28 of SPG11, close to the site in our study, was detected in an Iranian patient with HSP-TCC, suggesting that mutations in this area are not rare. Spatacsin is pivotal for autophagic lysosome reformation, a pathway that generates new lysosomes. Regeneration dysfunction of lysosomes from autolysosomes and impaired autophagic clearance were found in spatacsin knockout mice, suggesting that autophagy/lysosomal dysfunction was involved in the pathogenesis of SPG11. Our study expands the mutation spectrum of SPG11 and might help to determine the molecular mechanism of HSP-TCC.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We thank the family members for participating in the study, which was supported by the Natural Scientific Foundation of Shandong Province (ZR2013HQ016), Key Research and Development Project of Shandong Province (2015GGH318011), and Natural Scientific Foundation of Zhejiang Province (LY17H090002).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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