Our patient exhibited complex features together with delayed myelination, broadening the phenotypic spectrum of SPG56, and implying that CYP2U1 should be screened in HSP with delayed myelination.
There is no clear documentation of visual impairment in the few reported cases of SPG56, although this form is complex on clinical ground and visual deficit are extremely frequent in complicated HSP.
Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1 % for either CYP2U1 or DDHD2 and approximately 2 % for GBA2).
Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing.