Human Genetics

, Volume 122, Issue 3–4, pp 261–273

A novel locus for autosomal dominant “uncomplicated” hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3

  • Sylvain Hanein
  • Alexandra Dürr
  • Pascale Ribai
  • Sylvie Forlani
  • Anne-Louise Leutenegger
  • Isabelle Nelson
  • Marie-Claude Babron
  • Nizar Elleuch
  • Christel Depienne
  • Céline Charon
  • Alexis Brice
  • Giovanni Stevanin
Original Investigation

Abstract

Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous. Both “uncomplicated” and “complicated” forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Hitherto, ten autosomal dominant “uncomplicated” HSP (ADHSP) loci have been mapped. Here, we report linkage of ADHSP with markers of the 8p21.1-q13.3 chromosomal region in a large French family, including 29 examined at-risk individuals. The age at onset varied from 8 to 60 years with a mean of 31.6 ± 16.4 years. Multipoint and two-point LOD-score calculations as well as haplotype reconstruction in this region gave support to the location of this novel ADHSP locus (SPG37) in a 43.5 cM genetic interval flanked by loci D8S1839 and D8S1795. The region was shared by all definitely (n = 13), probably (n = 3) and possibly (n = 2) affected patients with a maximum LOD score of 4.20 at the D8S601 locus. Two candidate genes, encoding the kinesin family member 13B and neuregulin 1 (isoforms SMDF and GFF2), were screened for mutations, but no disease-causing alterations were identified. Interestingly, another region, on chromosome 10q22.3-23.31, was found to segregate in all affected patients (but not in probably or possibly affected subjects) and in a high proportion of healthy at risk individuals, suggesting that this locus might act as a modifier of the phenotype.

Supplementary material

439_2007_396_MOESM1_ESM.doc (24 kb)
Supplementary Material: Use of TLinkage (DOC 25 kb).

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sylvain Hanein
    • 1
    • 2
  • Alexandra Dürr
    • 1
    • 2
    • 3
  • Pascale Ribai
    • 1
    • 2
  • Sylvie Forlani
    • 1
    • 2
  • Anne-Louise Leutenegger
    • 4
    • 5
  • Isabelle Nelson
    • 1
    • 2
  • Marie-Claude Babron
    • 4
    • 5
  • Nizar Elleuch
    • 1
    • 2
  • Christel Depienne
    • 1
    • 2
    • 3
  • Céline Charon
    • 6
  • Alexis Brice
    • 1
    • 2
    • 3
    • 7
    • 8
  • Giovanni Stevanin
    • 1
    • 2
    • 3
  1. 1.INSERM, Unit 679, 47 Bd de l’HôpitalParisFrance
  2. 2.Institut Fédératif de Recherche en Neurosciences (IFR70), Groupe Hospitalier Pitié-SalpêtrièreUniversité Pierre et Marie Curie, Paris 6, UMR S679ParisFrance
  3. 3.Département de Génétique et CytogénétiqueAP-HP, Groupe Hospitalier Pitié-SalpêtrièreParisFrance
  4. 4.INSERM, U535VillejuifFrance
  5. 5.Univ. Paris-Sud, IFR69, UMR-S535VillejuifFrance
  6. 6.Centre National de GénotypageEvryFrance
  7. 7.Fédération de NeurologieAP-HP, Groupe Hospitalier Pitié-SalpêtrièreParisFrance
  8. 8.Faculté de Médecine, Groupe Hospitalier Pitié-SalpêtrièreUniversité Pierre et Marie Curie, Paris 6ParisFrance

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