Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

Clarice Patrono, Carlo Casali, Alessandra Tessa, Federica Cricchi, Daniela Fortini, Rosalba Carrozzo, Gabriele Siciliano, Enrico Bertini, Filippo M. Santorelli

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin.

Original languageEnglish
Pages (from-to)200-205
Number of pages6
JournalJournal of Neurology
Volume249
Issue number2
Publication statusPublished - 2002

Fingerprint

Paraplegia
Mutation
Mutation Rate
Age of Onset
Polymerase Chain Reaction
Genes

Keywords

  • Hereditary spastic paraplegia
  • Spastin
  • SPG4

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Patrono, C., Casali, C., Tessa, A., Cricchi, F., Fortini, D., Carrozzo, R., ... Santorelli, F. M. (2002). Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia. Journal of Neurology, 249(2), 200-205.

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia. / Patrono, Clarice; Casali, Carlo; Tessa, Alessandra; Cricchi, Federica; Fortini, Daniela; Carrozzo, Rosalba; Siciliano, Gabriele; Bertini, Enrico; Santorelli, Filippo M.

In: Journal of Neurology, Vol. 249, No. 2, 2002, p. 200-205.

Research output: Contribution to journalArticle

Patrono, C, Casali, C, Tessa, A, Cricchi, F, Fortini, D, Carrozzo, R, Siciliano, G, Bertini, E & Santorelli, FM 2002, 'Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia', Journal of Neurology, vol. 249, no. 2, pp. 200-205.
Patrono, Clarice ; Casali, Carlo ; Tessa, Alessandra ; Cricchi, Federica ; Fortini, Daniela ; Carrozzo, Rosalba ; Siciliano, Gabriele ; Bertini, Enrico ; Santorelli, Filippo M. / Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia. In: Journal of Neurology. 2002 ; Vol. 249, No. 2. pp. 200-205.
@article{19360fc3606344b89d879113ce21613c,
title = "Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia",
abstract = "We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin.",
keywords = "Hereditary spastic paraplegia, Spastin, SPG4",
author = "Clarice Patrono and Carlo Casali and Alessandra Tessa and Federica Cricchi and Daniela Fortini and Rosalba Carrozzo and Gabriele Siciliano and Enrico Bertini and Santorelli, {Filippo M.}",
year = "2002",
language = "English",
volume = "249",
pages = "200--205",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",
number = "2",

}

TY - JOUR

T1 - Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

AU - Patrono, Clarice

AU - Casali, Carlo

AU - Tessa, Alessandra

AU - Cricchi, Federica

AU - Fortini, Daniela

AU - Carrozzo, Rosalba

AU - Siciliano, Gabriele

AU - Bertini, Enrico

AU - Santorelli, Filippo M.

PY - 2002

Y1 - 2002

N2 - We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin.

AB - We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin.

KW - Hereditary spastic paraplegia

KW - Spastin

KW - SPG4

UR - http://www.scopus.com/inward/record.url?scp=0036166840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036166840&partnerID=8YFLogxK

M3 - Article

VL - 249

SP - 200

EP - 205

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

IS - 2

ER -