Objective: To report 4 families with hereditary spastic paraparesis due to CAPN1 mutations.

Background: Some years ago, CAPN1 mutations have been described as a cause of autosomal-recessive hereditary spastic paraparesis named SPG76. Few families with this disease have been reported in the literature and some authors consider it as a very rare entity. In Lille university medical center, four families have been identified with SPG76.

Method: Patients were screened through Next-Generation Sequencing using a multi-gene Illumina haloplex panel containing 144 genes related to spastic paraplegia and spastic ataxia, including CAPN1.

Results: We detected homozygosity for known pathogenic variants (Q527*, R339*) in three families, and a compound heterozygosity for two variants (G220R, IVS14), the latter being novel, in a fourth family. The R339*variant was present in two families originated from North Africa; with two distinct clinical patterns: severe lower-limb pyramidal syndrome and cerebellar ataxia. The frequency of CAPN1 mutation is 2% in our cohort.

Conclusion: SPG76 might be more common than expected and CAPN1 mutations should be more systematically screened, mainly for North African patients. Genotype-phenotype correlations need to be determined.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/capn1-mutations-are-more-common-than-expected-in-patients-with-hereditary-spastic-paraparesis/