Homozygous CAPN1 mutations causing a spastic-ataxia phenotype in 2 families

Abstract

Hereditary spastic paraplegias (HSPs) and ataxias are genetically heterogeneous disorders, with more than 70 genes implicated in each group. A smaller fraction of disorders from both groups manifest both with spastic paresis and ataxia, and recognizing this phenotype helps narrowing down the differential diagnosis.1 Recently, homozygous and compound heterozygous mutations in CAPN1, which encode for the neuronal cysteine protease calpain, have been described as a cause of HSP (SPG76, MIM#616907).2 Here, we report 3 patients from 2 families with homozygous CAPN1 mutations who are characterized with slowly progressive lower limb spasticity with mild ataxia. Review of all patients with CAPN1 mutations so far supports the strong association of cerebellar involvement with this disorder and delineates several additional disease characteristics.