LETTER TO THE EDITORS Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to L-DOPA treatment

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous. Pure forms are characterized primarily by progressive spasticity and weakness of the lower limbs. Complicated forms, however, involve neuro-nal systems other than corticospinal tracts, namely peripheral nerves, and sensory or cerebellar pathways [2]. At least 52 loci and 31 causative genes are known, and thus a gene-by-gene diagnostic approach is becoming imprac-tical. For the 19 autosomal dominant forms (AD-HSPs), 11 genes are known, with SPG4 being by far the most com-mon subtype (40–45 % AD-HSP cases) [4]. The vast het-erogeneity in HSP makes a genetic diagnosis difficult and expensive. Many research groups have used gene panels or targeted sequencing but the rapid growth and frequent identification of new genes makes this difficult