Identification of c.1495C > T mutation in SPAST gene in a family of Han Chinese with hereditary spastic paraplegia

Background: Hereditary spastic paraplegia 4 (SPG4) caused by spastin (SPAST) gene mutations accounts for 40-45% of hereditary spastic paraplegia (HSP) cases. To search for more genetic evidences for the pathogenesis of HSP, the SPAST genotype and clinical phenotype of a Chinese Han SPG4 family were analysed in this study.Methods: The clinical data of the proband and his family members were collected. Whole genomic DNA was extracted from peripheral blood, and the gene detection and pathogenicity analysis of mutations were conducted using whole-exome sequencing technology. Suspected pathogenic mutations were identified. Verification within this family was conducted by Sanger sequencing.Results: Eight (4 males and 4 females) of 20 members in 4 generations had SPG4. All patients presented with the high feet arches (pes cavus), the abnormal gait, the active tendon reflexes of the upper limbs, the hyperreflexia of the lower limbs, and the positive ankle clonus and Babinski's signs bilaterally. In the proband, we found a heterozygous mutation c.1495C > T in SPAST gene, which was associated with the autosomal dominant SPG4. Both the daughters and granddaughters of the proband in this family were verified to carry this mutation. The clinical characteristics of the SPG4 patients in this family are in line with the simple type of HSP. Heterozygous c.1495C > T is a pathogenic mutation in this family.Conclusion: In this study, we identified a c.1495C > T mutation in the SPAST gene in a Han Chinese family, enriching the mutation spectrum of SPG4.