Novel Pathogenic Variant of <i>ZFYVE26</i> in Hereditary Spastic Paraplegia

ABSTRACT We report a case of spastic paraplegia 15 (SPG15), a form of autosomal recessive hereditary spastic paraplegia, caused by compound heterozygous variants in the ZFYVE26 gene. A 27‐year‐old woman with no remarkable family history presented with intellectual disability since infancy and progressive gait disturbance beginning at age 12, later developing cerebellar ataxia and epilepsy. Brain MRI demonstrated a thin corpus callosum and a characteristic white matter hyperintensity known as the “ears of the lynx” sign. Whole‐genome sequencing identified two ZFYVE26 pathogenic variants: the previously reported (NM_015346.4:c.6775C⟩T, p.Q2259*) and the novel (NM_015346.4:c.1257C⟩A, p.C419*). These findings confirmed the SPG15 diagnosis. Given the clinical heterogeneity of SPG15, this case highlights the crucial role of next‐generation sequencing in achieving an early and accurate diagnosis.