Infancy onset hereditary spastic paraplegia associated with a novel atlastin mutation

The R495W mutation in SPG3A causes spastic paraplegia associated with axonal neuropathy

“…Although clinical examination did not reveal signs of peripheral neuropathy, neurophysiological studies showed a sensory-motor axonal neuropathy, a finding observed for the first time in atlastin-related HSP. Peripheral nerve electrophysiological examination, performed only in two previous studies [1,7], gave normal results.…”

“…Eight disease-causing mutations have so far been reported in SPG3A [1,4,[6][7][8]. Five missense mutations (R217Q, R239C, H247P, H258R, S259Y) have been found in exons 7 and 8, whereas one each is located in exon 4 (A161P) and 12 (M408V); one frameshift mutation has also been described in exon 12.…”

Cellular Localization, Oligomerization, and Membrane Association of the Hereditary Spastic Paraplegia 3A (SPG3A) Protein Atlastin

“…All but one of the reported atlastin-1 mutations in patients with SPG3A represent missense mutations; the other is a nucleotide insertion resulting in early termination in the C-terminal domain (13)(14)(15)(16). One missense mutation (R217Q) changes a highly conserved residue in the RD loop within the GTP-binding pocket of atlastin-1 and may thus alter GTP binding or GTPase activity (14).…”

“…Five missense mutations and one single base insertion with premature termination of the predicted 558-amino acid coding region of atlastin-1 have been reported (13)(14)(15)(16). It has been speculated that these mutations may alter the structure, interactions, or GTPase activity of atlastin-1 (13)(14)(15)(16). Of the members of the dynamin/Mx/ GBP superfamily, atlastin-1 is most similar to GBPs.…”

Extending the clinical spectrum of SPG3A mutations to a very severe and very early complicated phenotype

“…SPG3A is mainly associated with an early age of onset and a pure phenotype [1,3,4]. Recently a complicated SPG3A phenotype with axonal neuropathy has been reported [3,[5][6][7].…”