Exome Sequencing Identifies Novel Compound Heterozygous Mutations In SPG11That Cause Autosomal Recessive Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized byprogressive weakness and spasticity of the lower limbs, in complicated forms, withadditional neurological signs. To identify the genotype and characterize the phenotypein a Chinese HSP family, ten subjects from the family were examined through detailedclinical evaluations, auxiliary examinations and genetic tests. Using a combinedapproach of whole-exome sequencing and candidate mutation validation, we identifiednovel compound heterozygous mutations in the SPG11gene of the patients as follows: anonsense mutation c.6856C＞T (p.R2286X) in exon38and a deletion mutationc.2863delG (p.Glu955Lysfs*8) in exon16. Both mutations co-segregated with thephenotype in this family and were absent in100normal Chinese individuals. Ourfinding suggests that the novel compound heterozygous mutations in SPG11areassociated with HSP. We were able to assess the future risk of HSP in healthy youngerfamily members using genetic detection, and provide prenatal diagnoses for the familymembers. Furthermore, to some extent, this new finding enriches the information onSPG11and may provide a new basis for the genetic diagnosis of HSP.