Clinical and genetic analyses of 3 pedigrees with hereditary spastic paraplegia

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Objective To analyze the clinical manifestations and genetic mutations in 3 pedigrees with hereditary spastic paraplegia (HSP). Methods Three pedigrees diagnosed as having HSP in our hospital from January 2014 to November 2015, were chosen; the clinical manifestations, electrophysiology and imaging features of the patients in these three families were analyzed. Genomic DNA was extracted from peripheral venous blood, and the targeted gene capturing was employed to identify the disease-causing genes of these patients. Results The patients from the first family was familiar HSP, and the main clinical features were progressive lower limbs weakness and abnormal gait without cognitive impairment; the patients from the second family were familiar HSP and those from the third family were HSP without family history, and the main clinical features of the two pedigrees were slowly progressive spastic paraplegia and cognitive impairment. In addition, thin corpus callosum was visible in MR imaging of family three. Genetic testing showed the first family presented with a known mutation c.715C>T of ATL1 exon 7 and the loci co-segregated in the family. The second family presented with novel compound heterozygous mutations in the SPG11 gene: c.3099_3103delGTTTG mutation of exon 17and c3817_3818insTGA mutation of exon 22; novel compound heterozygous mutations in the SPG11 gene in the third family were detected as follows: c.6194C>G mutation of exon 32 and c.5121+1C>T splicing mutation of intro 29. Conclusions Four novel mutations in SPG11 gene and one known mutation in ATL1 gene are found, which enriches the known HSP mutation types.Targeted gene capture is an efficient and rapid tool for identifying the causation of some complex and genetically heterogeneous neurodegenerative diseases. Key words: Hereditary spastic paraplegia; Targeted gene capturing; ATL1 gene; SPG11 gene