Report of three cases with hereditary spastic paraplegia and investigation of the mutations

Hereditary spastic paraplegia (HSP) includes a group of clinically and genetically heterogeneous disorders with multiple genetic loci participating in its pathogenesis. Here we report three Iranian patients with HSP. Molecular analyses revealed that they have mutations in AP4M1 gene (NM_004722: c.802C > T, p.R268X and c.1225T > C, p.F409L) and AP4E1 gene (NM_007347: c.3212_3213delCT, p.L1072Afs* 10). All of them were born to consanguineous parents. Genetic diagnosis was performed using whole exome sequencing (WES), Sanger sequencing and segregation analysis. Due to heterogeneity in clinical manifestations and inheritance mode as well as the presence of different causative genes in HSP, WES facilitates the diagnosis and provides opportunity for prenatal diagnosis in families with affected members.