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

A. Magariello, M. Muglia, A. Patitucci, C. Ungaro, R. Mazzei, A.L. Gabriele, T. Sprovieri, L. Citrigno, F.L. Conforti, M. Liguori, A Gambardella, F. Bono, T. Piccoli, F. Patti, M. Zappia, M. Mancuso, F. Iemolo, A. Quattrone

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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. 

Original languageEnglish
Pages (from-to)96-100
Number of pages5
JournalJournal of the Neurological Sciences
Volume288
Issue number1-2
DOIs
Publication statusPublished - 15 Jan 2010

Keywords

  • 3 ' UTR
  • CLASSIFICATION
  • COLLECTION
  • EXON DELETIONS
  • EXPRESSION ANALYSIS
  • FAMILIES
  • FREQUENT
  • Hereditary spastic paraplegia
  • MLPA
  • Mutation analysis
  • SPECTRUM
  • SPG4

Cite this

Magariello, A., Muglia, M., Patitucci, A., Ungaro, C., Mazzei, R., Gabriele, A. L., ... Quattrone, A. (2010). Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. Journal of the Neurological Sciences, 288(1-2), 96-100. https://doi.org/10.1016/j.jns.2009.09.025
Magariello, A. ; Muglia, M. ; Patitucci, A. ; Ungaro, C. ; Mazzei, R. ; Gabriele, A.L. ; Sprovieri, T. ; Citrigno, L. ; Conforti, F.L. ; Liguori, M. ; Gambardella, A ; Bono, F. ; Piccoli, T. ; Patti, F. ; Zappia, M. ; Mancuso, M. ; Iemolo, F. ; Quattrone, A. / Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. In: Journal of the Neurological Sciences. 2010 ; Vol. 288, No. 1-2. pp. 96-100.
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title = "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 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. ",
keywords = "3 ' UTR, CLASSIFICATION, COLLECTION, EXON DELETIONS, EXPRESSION ANALYSIS, FAMILIES, FREQUENT, Hereditary spastic paraplegia, MLPA, Mutation analysis, SPECTRUM, SPG4",
author = "A. Magariello and M. Muglia and A. Patitucci and C. Ungaro and R. Mazzei and A.L. Gabriele and T. Sprovieri and L. Citrigno and F.L. Conforti and M. Liguori and A Gambardella and F. Bono and T. Piccoli and F. Patti and M. Zappia and M. Mancuso and F. Iemolo and A. Quattrone",
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Magariello, A, Muglia, M, Patitucci, A, Ungaro, C, Mazzei, R, Gabriele, AL, Sprovieri, T, Citrigno, L, Conforti, FL, Liguori, M, Gambardella, A, Bono, F, Piccoli, T, Patti, F, Zappia, M, Mancuso, M, Iemolo, F & Quattrone, A 2010, 'Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia', Journal of the Neurological Sciences, vol. 288, no. 1-2, pp. 96-100. https://doi.org/10.1016/j.jns.2009.09.025

Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. / Magariello, A.; Muglia, M.; Patitucci, A.; Ungaro, C.; Mazzei, R.; Gabriele, A.L.; Sprovieri, T.; Citrigno, L.; Conforti, F.L.; Liguori, M.; Gambardella, A; Bono, F.; Piccoli, T.; Patti, F.; Zappia, M.; Mancuso, M.; Iemolo, F.; Quattrone, A.

In: Journal of the Neurological Sciences, Vol. 288, No. 1-2, 15.01.2010, p. 96-100.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia

AU - Magariello, A.

AU - Muglia, M.

AU - Patitucci, A.

AU - Ungaro, C.

AU - Mazzei, R.

AU - Gabriele, A.L.

AU - Sprovieri, T.

AU - Citrigno, L.

AU - Conforti, F.L.

AU - Liguori, M.

AU - Gambardella, A

AU - Bono, F.

AU - Piccoli, T.

AU - Patti, F.

AU - Zappia, M.

AU - Mancuso, M.

AU - Iemolo, F.

AU - Quattrone, A.

PY - 2010/1/15

Y1 - 2010/1/15

N2 - 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. 

AB - 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. 

KW - 3 ' UTR

KW - CLASSIFICATION

KW - COLLECTION

KW - EXON DELETIONS

KW - EXPRESSION ANALYSIS

KW - FAMILIES

KW - FREQUENT

KW - Hereditary spastic paraplegia

KW - MLPA

KW - Mutation analysis

KW - SPECTRUM

KW - SPG4

U2 - 10.1016/j.jns.2009.09.025

DO - 10.1016/j.jns.2009.09.025

M3 - Article

VL - 288

SP - 96

EP - 100

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1-2

ER -