Key Scientific Papers

The discovery (2016)

• Mutations in CAPN1 cause autosomal-recessive hereditary spastic paraplegiaGan-Or Z, et al. American Journal of Human Genetics, 2016Identified CAPN1 mutations in three families with recessive hereditary spastic paraplegia and named the condition SPG76.
• Defects in the CAPN1 gene result in alterations in cerebellar development and in cerebellar ataxia in mice and humansWang Y, et al. Cell Reports, 2016Showed that loss of CAPN1 disturbs development of the cerebellum and causes ataxia in mice and in people.

The clinical picture

• Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlationsMéreaux J-L, et al. Neurogenetics, 2021A review of CAPN1 variants across spastic ataxias and how the genetic change relates to symptoms.
• Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxiaLai L-L, et al. Annals of Clinical and Translational Neurology, 2020New CAPN1 mutations, showing how varied the combined spastic paraplegia and ataxia picture can be.
• Two novel homozygous mutations of CAPN1 in Chinese patients with hereditary spastic paraplegia and literatures reviewPeng F, et al. Orphanet Journal of Rare Diseases, 2019Two new CAPN1 mutations, with a review of earlier published cases.
• Homozygous CAPN1 mutations causing a spastic-ataxia phenotype in 2 familiesKocoglu C, et al. Neurology: Genetics, 2018Two families with homozygous CAPN1 mutations and a combined spastic-ataxia picture.
• A novel CAPN1 mutation causes a pure hereditary spastic paraplegia in an Italian familyCotti Piccinelli S, et al. Frontiers in Neurology, 2019A new CAPN1 mutation causing a pure form of hereditary spastic paraplegia.
• CAPN1 variants as cause of hereditary spastic paraplegia type 76Garcia-Berlanga JE, et al. Case Reports in Neurological Medicine, 2019A case report of SPG76 caused by CAPN1 variants.
• Novel CAPN1 missense variants in complex hereditary spastic paraplegia with early-onset psychosisAlecu JE, et al. Annals of Clinical and Translational Neurology, 2022New CAPN1 missense variants in a complex form of hereditary spastic paraplegia.
• Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvementLan M-Y, et al. Frontiers in Neurology, 2022The clinical and genetic picture of spastic paraparesis with cerebellar involvement in a Taiwanese cohort.

Laboratory models and the calpain pathway

• A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activationLiu Y, et al. Neuropharmacology, 2016In mice lacking calpain-1, a low dose of a selective calpain-2 inhibitor restored normal learning.
• Generation of an integration-free induced pluripotent stem cell line, FJMUi001-A, from a hereditary spastic paraplegia patient carrying compound heterozygous p.P498L and p.R618W mutations in CAPN1 (SPG76)Lu Y-Q, et al. Stem Cell Research, 2019A stem-cell line made from an SPG76 patient's cells, for laboratory research.
• Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxiaMenden B, et al. Nature Communications, 2026Loss of CD99L2, a protein that switches on calpain-1, causes a related X-linked spastic ataxia.

This list is selective and will grow. The foundation does not provide medical advice.