SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum.
We studied in more detail the SPG5-related spectrum of complex phenotypes by screening CYPB1 for mutations in a large cohort of 105 Italian hereditary spastic paraplegias (HSPs) index patients including 50 patients with a complicated HSP (cHSP) phenotype overlapping the SPG11- and the SPG15-related forms except for the lack of thin corpus callosum and 55 pure patients.
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes.
This finding, together with the report of a mutation in another Italian family, provides confirmation that ZFYVE26 is the second gene responsible for ARHSP-TCC in the Italian population.