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Case Reports
. 2016 Jun 3:16:87.
doi: 10.1186/s12883-016-0604-5.

A case report of SPG11 mutations in a Chinese ARHSP-TCC family

Linwei Zhang  1   2 , Karen N McFarland  2 , Jinsong Jiao  1 , Yujuan Jiao  3
Affiliations
Case Reports

A case report of SPG11 mutations in a Chinese ARHSP-TCC family

Linwei Zhang et al. BMC Neurol. .

Abstract

Background: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a complicated form of hereditary spastic paraplegia, characterized by progressive spastic paraplegia, weakness of the lower extremities and is usually accompanied by mental retardation. Mutations in the Spastic Paraplegia gene 11 (SPG11) account for a large proportion of ARHSP-TCC cases worldwide.

Case presentation: We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. We performed detailed physical and auxiliary examinations and were able to exclude acquired causes of spastic paraplegia. To determine the causative mutation, we took a candidate gene approach and screened the coding sequence and some flanking intronic sequence of SPG11 by direct Sanger sequencing. We identified two novel compound heterozygous mutations in SPG11 in affected individuals (c.1551_1552delTT, p.Cys518SerfsTer39 and c.5867-1G > T (IVS30-1G > T), p.Thr1956ArgfsTer15). Bioinformatic analysis predicts that these mutations would lead to a loss of protein function due to the truncation of the SPG11 protein.

Conclusions: The results of this case report indicate a broader approach to include screening for SPG11 mutations in ARHSP-TCC patients. Our findings enrich the phenotypic spectrum of SPG11 mutations.

Keywords: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (ARHSP-TCC); Gene mutation; Heterozygous mutations; SPG11.

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Figures

Fig. 1
Fig. 1
Family pedigree of non-conanguineous parents indicating segregation of SPG11 mutations. Squares, male; circles, female; filled circle, affected female; arrow, proband
Fig. 2
Fig. 2
Presentation of pes cavus in the index patient (II:3)
Fig. 3
Fig. 3
Sagittal brain and thoracic spinal MRI image in index patient (II:3). a: Brain MRI shows thinning of corpus callosum, emphasized in the anterior part with a “beaked” shape (arrow). Ther is no obvious periventricular or deep cerebellar white matter lesions and no obvious cerebral or cerebellar atrophy. b: Throracic spinal MRI shows thinning of the thoracic spinal cord with volume loss but no obvious signal abnormalities in the cord
Fig. 4
Fig. 4
Sanger sequencing of exon 7 (c.1551_1552delTT) containing a TT deletion in SPG11 in an affected individual (a) and unaffected individual (b). Sanger sequencing of a splice site mutation (c.5867-1G > T (IVS30-1G > T)) in intron 30 of SPG11 in an affected individual (c) and control, unaffected (d)
Fig. 5
Fig. 5
Bioinformatic prediction of the SPG11 protein structure in the presence of the found mutations. Boxes in blue indicate the exons of the SPG11 major transcripts (NM_025137 and NM_001160227). The location of the mutations described in this study are located in exon 7 (c.1551_1552delTT) and upstream of exon 31 (c.5867-1G > T (IVS30-1G > T)). Boxes in grey indicate the predicated protein truncations (middle and lower) as compared with a full-length wild-type structure (upper)
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