Novel nonsense SPG11 likely pathogenic variant: c.3115C>T, p.Gln1039Ter

Here we report a novel likely pathogenic mutation of SPG11 in a patient affected by HSP The proband, a 29-year-old individual, exhibited a rapid progression of spastic paraparesis and mild cognitive impairment. Brain MRI showed classical (e.g., TCC and “ears of the lynx” sign) and atypical features such as cerebellar atrophy. A targeted NGS panel covering HSP-related genes revealed two heterozygous variants in SPG11(NM_025137): c.2849dupT, p.Leu950PhefsTer4 (pathogenic), and c.3115C>T, p.Gln1039Ter. The latter variant has not been previously reported, fulfilled ACMG criteria PSV1, PM2 and PM3, and was therefore classified as likely pathogenic. Segregation analysis confirmed that the two SPG11 variants were inherited from different parents, consistent with compound heterozygous state.