Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: A novel mutation in the SPG11 gene and further evidence for genetic heterogeneity

T. Pippucci, E. Panza, E. Pompilii, V. Donadio, A. Borreca, C. Babalini, C. Patrono, R. Zuntini, T. Kawarai, G. Bernardi, R. Liguori, G. Romeo, P. Montagna, A. Orlacchio, M. Seri

Research output: Contribution to journalArticle

Abstract

Background and purpose: Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 (SPG11) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous. Methods: Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals. Results: Linkage was excluded in the four consanguineous families. In the only SPG11-linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene. Discussion: This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalEuropean Journal of Neurology
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Hereditary spastic paraplegia
  • Linkage analysis
  • SPG11
  • Splice site mutations
  • Thinning of the corpus callosum

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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