A novel homozygous mutation in ERLIN1 gene causing spastic paraplegia 62 and literature review

Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP. Herein, we report the case of the first Chinese SPG62 patient, explore the potential pathogenic mechanism and review ERLIN1-related HSP patients. A 23-year-old man had progressive difficulty in walking and gait abnormalities for more than 11 years. Physical examination showed slightly reduced muscle strength (5^-/5) and elevated muscle tone in the lower limbs and hyperreflexia in four limbs. Genetic analysis identified a novel splicing site mutation in ERLIN1 gene (c.504+1G > A), which was predicted to disturb the normal splicing process of mRNA by bioinformatic tools. Minigene experiment further confirmed the mutation c.504+1G > A could cause erroneous deletion of Exon 7 in the mRNA, which may change the conserved prohibitin (PHB) domain of erlin-1 and affect the function of erlin1/2 complex. Thus, we identified a pathogenic mutation of ERLIN1 splicing site causing delayed-onset pure HSP. This study widened the genetic and phenotypic spectrum of SPG62.