HSP with no family history

Posted - March 2007 in Research Highlights

Gene testing should be done where HSP occurs without family history.

The unexpected presence of SPG4 gene mutations in patients with sporadic spastic paraplegia suggests that gene testing should be done in individuals with pure or complicated spastic paraplegia without family histories.

BACKGROUND: SPG4 encodes spastin, a member of the AAA protein family, and is the major gene responsible for autosomal dominant spastic paraplegia. It accounts for 10-40% of families with pure (or eventually complicated) hereditary spastic paraparesis (HSP).

OBJECTIVE: To assess the frequency of SPG4 mutation in patients with spastic paraplegia but without family histories.

METHODS: 146 mostly European probands [senior family member with HSP] with progressive spastic paraplegia were studied (103 with pure spastic paraplegia and 43 with additional features). Major neurological causes of paraplegia were excluded. None had a family history of paraplegia.

RESULTS: The overall rate of mutations was 12%; 19 different mutations were identified in 18 patients, 13 of which were novel. In one family, where both parents were examined and found to be normal, the mutation was transmitted by the asymptomatic mother, indicating reduced penetrance. The parents of other patients were not available for analysis but were reported to be normal. There was no evidence for de novo mutations. The mutations found in these apparently isolated patients were mostly of the missense type and tended to be associated with a less severe phenotype than previously described in patients with inherited mutations.

J Med Genet. 2006 Mar;43(3):259-65. Epub 2005 Jul 31.

Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases.

Depienne C, Tllaksen C, Lephay JY, Bricka B, Poea-Guyon S, Fontaine B, Labauge P, Brice A, Durr A.