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

• 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
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2009.09.025

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.