neurogenetics

, Volume 11, Issue 4, pp 441–448

A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum

Authors

    • Department of NeurologyHabib Bourguiba University Hospital
    • Faculté de Médecine de Sfax
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
    • AP-HP, Pitié-Salpêtrière HospitalDepartment of Genetics and Cytogenetics
    • Service de NeurologieHôpital Habib Bourguiba
  • Imed Feki
    • Department of NeurologyHabib Bourguiba University Hospital
    • Faculté de Médecine de Sfax
  • Nizar Elleuch
    • Department of NeurologyHabib Bourguiba University Hospital
    • Faculté de Médecine de Sfax
  • Mohamed Imed Miladi
    • Department of NeurologyHabib Bourguiba University Hospital
    • Faculté de Médecine de Sfax
  • Anne Boland-Augé
    • Centre National de Génotypage
  • Jérémy Truchetto
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
  • Emeline Mundwiller
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
  • Nadia Jezequel
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
  • Diana Zelenika
    • Centre National de Génotypage
  • Chokri Mhiri
    • Department of NeurologyHabib Bourguiba University Hospital
    • Faculté de Médecine de Sfax
  • Alexis Brice
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
    • AP-HP, Pitié-Salpêtrière HospitalDepartment of Genetics and Cytogenetics
  • Giovanni Stevanin
    • INSERM, U975 (formerly U679)
    • Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, CNRS 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle EpinièreGroupe Hospitalier Universitaire Pitié-Salpêtrière
    • AP-HP, Pitié-Salpêtrière HospitalDepartment of Genetics and Cytogenetics
    • Ecole Pratique des Hautes Etudes
Original Article

DOI: 10.1007/s10048-010-0249-2

Cite this article as:
Boukhris, A., Feki, I., Elleuch, N. et al. Neurogenetics (2010) 11: 441. doi:10.1007/s10048-010-0249-2

Abstract

Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.

Keywords

Hereditary spastic paraplegiaAutosomal recessiveThin corpus callosumLinkageSPG46

Copyright information

© Springer-Verlag 2010