Spastizin mutation in hereditary spastic paraplegia with thin corpus callosum

Hereditary spastic paraplegias (HSPs) are a group of clinically and genetically diverse neurological disorders characterized by progressive and generally severe spasticity and weakness of the lower extremity [1]. It is a rare heterogeneous disease with an overall prevalence of 1–10 in 100,000 individuals and affects diverse ethnic groups [1]. HSP with thin corpus callosum (AR-HSP-TCC) is an autosomal recessive disorder classified as complex subtype of HSP with additional clinical features [2, 3]. Most of the complex AR-HSP-TCC subtypes are reported with mutations in the genes KIAA1840 (SPG11) and ZFYVE26 (SPG15) encoding proteins spatacsin and spastizin, respectively, with almost identical clinical features [4–7]. Spastizin, a FYVE family of zinc finger binding domain containing protein, primarily expressed in neurons and involved in lysosomal biogenesis [8]. Previously, three independent case studies have been reported in individuals with AR-HSP-TCC from the Indian subcontinent [9–11] and one of the studies reported homozygous KIAA1840 (SPG11) gene mutation in a patient [11]. We describe mutation profile in a proband and in parents with ZFYVE26 mutation identified by targeted exome sequencing with spasticity in both lower limb and progressive thinning of the corpus callosum (TCC).