Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia

Abstract Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12–18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evid...

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Published in:	Journal of the neurological sciences Vol. 288; no. 1; pp. 96 - 100
Main Authors:	Magariello, Angela, Muglia, Maria, Patitucci, Alessandra, Ungaro, Carmine, Mazzei, Rosalucia, Gabriele, Anna Lia, Sprovieri, Teresa, Citrigno, Luigi, Conforti, Francesca Luisa, Liguori, Maria, Gambardella, Antonio, Bono, Francesco, Piccoli, Tommaso, Patti, Francesco, Zappia, Mario, Mancuso, Michelangelo, Iemolo, Franco, Quattrone, Aldo
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 15-01-2010 Elsevier
Subjects:	3' Untranslated Regions - genetics 3′ UTR Adenosine Triphosphatases - genetics Adolescent Adult Aged Biological and medical sciences Child Chromatography, High Pressure Liquid Cohort Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases DNA Mutational Analysis Exons Female Gene Deletion Genotype Hereditary spastic paraplegia Humans Italy Male Medical sciences Middle Aged MLPA Mutation analysis Mutation, Missense - genetics Neurology Paraplegia - genetics Phenotype Reverse Transcriptase Polymerase Chain Reaction Spastin SPG4 Young Adult Italy Hereditary spastic paraplegia Mutation analysis MLPA SPG4 3′ UTR Human Italian Nervous system diseases Genetic disease Cerebral disorder Central nervous system disease Complication Degenerative disease Mutation 3' UTR Spinal cord disease
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Summary:	Abstract Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12–18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene. We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c.1656_1664delinsTGACCT, c.1688-3C>G and c.*2G>T) and two exon deletions previously reported. The overall rate of SPG4 gene mutation in our patients was 36.8% (14/38); in AD-HSP we observed a mutation frequency of 45.8% (11/24), in sporadic cases the frequency was 21.4% (3/14). Furthermore, we found a mutational rate of 22.2% (2/9) and 41.4% (12/29) in the complicated and pure forms, respectively. The results underlie the importance of genetic testing in all affected individuals.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-510X 1878-5883
DOI:	10.1016/j.jns.2009.09.025