+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Detection of novel mutations and review of published data suggests that hereditary spastic paraplegia caused by spastin (SPAST) mutations is found more often in males



Detection of novel mutations and review of published data suggests that hereditary spastic paraplegia caused by spastin (SPAST) mutations is found more often in males



Journal of the Neurological Sciences 306(1-2): 62-65



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. 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. 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). 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 036083638

Download citation: RISBibTeXText

PMID: 21546041

DOI: 10.1016/j.jns.2011.03.043


Related references

Truncating mutations of SPAST associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin. Molecular Biology of the Cell 28(13): 1728-1737, 2017

Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations. Journal of Neurology, Neurosurgery, and Psychiatry 81(10): 1073-1078, 2010

SPAST mutations in Australian patients with hereditary spastic paraplegia. Internal Medicine Journal 42(12): 1342-1347, 2013

Mutation analysis of the spastin gene in hereditary spastic paraplegia type 4 Evidence of aberrant transcript splicing caused by mutations in noncanonical splice site sequences. American Journal of Human Genetics 67(4 Suppl. 2): 375, 2000

Two novel mutations in the Spastin gene of Chinese patients with hereditary spastic paraplegia. European Journal of Neurology 18(9): 1194-1196, 2012

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia. Neuromuscular Disorders 16(6): 387-390, 2006

Frequency of Spastin mutations in German pedigrees with hereditary spastic paraplegia. American Journal of Human Genetics 69(4 Suppl.): 599, 2001

Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations. Neurogenetics 5(3): 157-164, 2004

Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia. Archives of Neurology 61(1): 49-55, 2004

Spastin gene mutations in Bulgarian patients with hereditary spastic paraplegia. Clinical Genetics 70(6): 490-495, 2006

A patient-derived stem cell model of hereditary spastic paraplegia with SPAST mutations. Disease Models and Mechanisms 8(10): 1339, 2015

Novel human pathological mutations. Gene symbol: SPAST. Disease: Hereditary spastic paraplegia. Human Genetics 127(1): 112, 2010

A patient-derived stem cell model of hereditary spastic paraplegia with SPAST mutations. Disease Models and Mechanisms 6(2): 489-502, 2013

Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. American Journal of Human Genetics 68(5): 1077-1085, 2001

Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia. Journal of the Neurological Sciences 201(1-2): 65-69, 2002