Hereditary spastic paraplegia: Novel mutations and expansion of the phenotype variability in SPG56

We describe a novel sporadic case of SPG56, a rare complicated form of HSP, that expands the clinical and molecular spectrum of the disease, being associated to novel mutations in CYP2U1 and showing as novel feature dorsal hydromyelia at spinal cord MRI. The patient presented an early-onset, slowly progressive paraparesis associated with mild mental retardation. Neurological assessments included the Spastic Paraplegia Rating Scale (SPRS), Mental Deterioration Battery (MDB), and Wechsler Adult Intelligence Scale (WAIS), neurophysiological and neuroimaging studies. Targeted next-generation sequencing panels for the whole set of genes associated with HSP were performed in the probands and her relatives. Neuroimaging studies showed dorsal hydromyelia but no brain MRI abnormalities. Targeted next-generation identified two novel mutations: the c.5C > A/p.S2* on the maternal allele in compound heterozygosity with the paternally-inherited c.1288+5G > C in CYP2U1. Both mutations predict early protein truncation and a loss of function. So far, only few SPG56 cases have been reported. This case, expands and further characterize the clinical and molecular spectrum of SPG56. In this regard, in consideration of the putative gene function in neurodevelopment, we suggest a causal association between CYP2U1 mutations and hydromyelia in our patient.