Abstract
Background
Hereditary spastic paraplegia (HSP) is characterised in its pure form by slowly progressive
spastic paraparesis. Around 40% of autosomal dominant (AD) cases are caused by mutations
in SPAST, encoding spastin.
Patients and methods
The clinical and investigation details of all patients with a SPAST mutation identified through our centre were reviewed. All published reports of SPAST mutations where the sex of patients was given were subsequently analysed in order
to determine whether there is evidence of one sex being preferentially affected.
Results
In total 22 probable pathogenic changes were detected, including 11 novel ones. One
patient carried two adjacent missense mutations. The pathogenicity of a further novel
missense mutation is uncertain. Most patients had a pure phenotype, although mild
peripheral neuropathy was sometimes present. The total number of patients with SPAST mutations was 27, as three of the previously known mutations were present in more
than one person. The excess of males over females in our population (17:10) prompted
us to review all published studies where the sex of the patients was given (n=31). A significant excess of males was identified (ratio 1.29, p=0.0007).
Conclusions
Our results are consistent with data suggesting that SPAST mutations mostly cause a pure HSP phenotype. The excess of males in our sample and
in published reports suggests that penetrance or severity may be sex-dependent, and
merits further investigation as it may have important implications for counselling.
Keywords
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Article info
Publication history
Published online: May 06, 2011
Accepted:
March 28,
2011
Received in revised form:
February 8,
2011
Received:
November 28,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
