, Volume 260, Issue 9, pp 2414-2416,
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Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to l-DOPA treatment

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Dear Sirs,

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 neuronal 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 impractical. For the 19 autosomal dominant forms (AD-HSPs), 11 genes are known, with SPG4 being by far the most common subtype (40–45 % AD-HSP cases) [4]. The vast heterogeneity 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.

We studied a female patient presenting familial spastic paraplegia with sensory axonal neuropathy, compatible with AD inheritance (Fig. 1a). At the age of 10 years