Clinical characteristics and gene mutation analysis of a family with hereditary spastic paraplegia type 11: a case...

Autosomal recessive hereditary spastic paraplegia with thinning of the corpus callosum is a complex hereditary spastic paraplegia. Spastic paraplegia type 11 (SPG11) mutation is the most frequent form of autosomal recessive hereditary spastic paraplegia with thinning of the corpus callosum. The study of SPG11 in China is small scale, and only a few gene mutations have been reported.

We report the case of a family with autosomal recessive hereditary spastic paraplegia with thinning of the corpus callosum. We describe a 20-year-old Han female patient with spastic gait and cognitive impairment 2 years ago, whose brain imaging revealed a thinning corpus callosum. Her 14-year-old Han brother had only a spasmodic gait. Detailed history, physical examination, and supplementary examination were performed to rule out the cause of spastic paraplegia. To identify pathogenic mutations, we used target sequence capture sequencing technology to detect hereditary-spastic-paraplegia-related genes in family members in combination with Sanger sequencing. We found two new complex heterozygous mutations in SPG11: c.6738_6739insT and c.5934_5935insTAACCTGGAA. The Glu2247 amino acid codon was changed to a stop codon (p.Glu2247Ter), and the Val1979 amino acid was also changed to a stop codon (p. Val1979Ter). Bioinformatics analysis predicted that these mutations would result in a loss of protein function. In silico analysis of the mutant sequences was performed.

We found two novel complex heterozygous mutations, c.6738_6739insT and c.5934_5935insTAACCTGGAA, which enriched the phenotypic spectrum of SPG11 mutations related to hereditary spastic paraplegia and may help to determine the molecular mechanism of hereditary spastic paraplegia with thinning of the corpus callosum.