SPG11: a consistent clinical phenotype in a family with homozygous spatacsin truncating mutation

Abstract

Hereditary spastic paraplegias (HSP) are a heterogeneous group of neurodegenerative disorders leading to progressive spasticity of the lower limbs. Here, we describe clinical and genetic features in an Italian family affected by autosomal recessive HSP (ARHSP) with mental impairment and thin corpus callosum (TCC). In both affected subjects, genetic analysis revealed the presence of a homozygous small deletion (733_734delAT) leading to a frameshift (M245VfsX) within the coding region of SPG11 gene, encoding spatacsin. This finding is the first independent confirmation that spatacsin loss of function mutations cause ARHPS-TCC.