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

摘要

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