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Exon Deletions of SPG4 are a Frequent Cause of Hereditary Spastic Paraplegia
  1. Christel Depienne (depienne{at}ccr.jussieu.fr)
  1. INSERM U679, France
    1. Estelle Fedirko (fedirko{at}ccr.jussieu.fr)
    1. Département de Génétique, Cytogénétique et Embryologie, AP-HP, France
      1. Sylvie Forlani (sforlani{at}ccr.jussieu.fr)
      1. INSERM U679, France
        1. Cécile Cazeneuve (cecile.cazeneuve{at}psl.ap-hop-paris.fr)
        1. Département de Génétique, Cytogénétique et Embryologie, AP-HP, France
          1. Pascale Ribaï (ribai{at}ccr.jussieu.fr)
          1. INSERM U679, France
            1. Imed Feki (imed_feki{at}yahoo.fr)
            1. INSERM U679, France
              1. Chantal Tallaksen (chantal.tallaksen{at}ulleval.no)
              1. INSERM U679, France
                1. Karine Nguyen (karine.nguyen{at}ap-hm.fr)
                1. Hôpital de la Timone, Marseille, France
                  1. Bruno Stankoff (bruno.stankoff{at}psl.ap-hop-paris.fr)
                  1. Fédération des Maladies du Système Nerveux, France
                    1. Merle Ruberg (ruberg{at}ccr.jussieu.fr)
                    1. INSERM U679, France
                      1. Giovanni Stevanin (stevanin{at}ccr.jussieu.fr)
                      1. INSERM U679, France
                        1. Alexandra Durr (durr{at}ccr.jussieu.fr)
                        1. INSERM U679, France
                          1. Alexis Brice (brice{at}ccr.jussieu.fr)
                          1. INSERM U679, France

                            Abstract

                            Background: Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). Standard methods for genetic analyses miss, however, exonic microdeletions.

                            Objective and Methods: We screened 121 mutation-negative probands for rearrangements in SPG4 by multiplex ligation-dependent probe amplification (MLPA).

                            Results: We identified 24 patients with 16 different heterozygous exon deletions in SPG4 (20%) ranging from one exon to the whole coding sequence. Comparison with 78 patients with point mutations showed a similar clinical picture but earlier age at onset.

                            Conclusions: These results indicate that exon deletions in SPG4 are as frequent as point mutations and that SPG4 is responsible for 40% of AD-HSP.

                            • HSP
                            • MLPA
                            • SPAST
                            • SPG4
                            • microdeletion

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