neurogenetics

, Volume 11, Issue 3, pp 313–318

Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19

  • K. G. Meilleur
  • M. Traoré
  • M. Sangaré
  • A. Britton
  • G. Landouré
  • S. Coulibaly
  • B. Niaré
  • F. Mochel
  • A. La Pean
  • I. Rafferty
  • C. Watts
  • D. Shriner
  • M. T. Littleton-Kearney
  • C. Blackstone
  • A. Singleton
  • K. H. Fischbeck
ORIGINAL ARTICLE

Abstract

We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43.

Keywords

Hereditary spastic paraplegia Amyotrophy Autosomal recessive Chromosome 19 SPG43 

References

  1. 1.
    Hanein S, Martin E, Boukhris A et al (2008) Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet 82:992–1002CrossRefPubMedGoogle Scholar
  2. 2.
    Dürr A (2008) Genetic testing for the spastic paraplegias: drowning by numbers. Neurology 71:236–238CrossRefPubMedGoogle Scholar
  3. 3.
    Leutenegger A, Labalme A, Génin E, Toutain A, Steichen E, Clerget-Darpoux F, Edery P (2006) Using genomic inbreeding coefficient estimates for homozygosity mapping of rare recessive traits: application to Taybi-Linder syndrome. Am J Hum Genet 79:62–66CrossRefPubMedGoogle Scholar
  4. 4.
    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575CrossRefPubMedGoogle Scholar
  5. 5.
    Geppert M, Goda Y, Stevens CF, Sudhof TC (1997) The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 387:810–814CrossRefPubMedGoogle Scholar
  6. 6.
    Harter C, Wieland FT (1998) A single binding site for dilysine retrieval motifs and p23 within the gamma subunit of coatomer. Proc Natl Acad Sci USA 95:11649–11654CrossRefPubMedGoogle Scholar
  7. 7.
    Nielsen JV, Mitchelmore C, Pedersen KM et al (2004) FKBP8: novel isoforms, genomic organization, and characterization of a forebrain promoter in transgenic mice. Genomics 83:181–192CrossRefPubMedGoogle Scholar
  8. 8.
    Shirane M, Nakayama KI (2006) Protrudin induces neurite formation by directional membrane trafficking. Science 314:818–821CrossRefPubMedGoogle Scholar
  9. 9.
    Martignoni M, Riano E, Rugarli EI (2008) The role of ZFYVE27/protrudin in hereditary spastic paraplegia. Am J Hum Genet 83:127–128, author reply 128-30CrossRefPubMedGoogle Scholar
  10. 10.
    Lander ES, Botstein D (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236:1567–1570CrossRefPubMedGoogle Scholar
  11. 11.
    Gibbs JR, Singleton A (2006) Application of genome-wide single nucleotide polymorphism typing: simple association and beyond. PLoS Genet 2:e150CrossRefPubMedGoogle Scholar
  12. 12.
    Garshasbi M, Motazacker MM, Kahrizi K et al (2006) SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly. Hum Genet 118:708–715CrossRefPubMedGoogle Scholar
  13. 13.
    Morrow EM, Yoo SY, Flavell SW et al (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218–223CrossRefPubMedGoogle Scholar
  14. 14.
    Camargos S, Scholz S, Simon-Sanchez J et al (2008) (2008) DYT16, a novel young-onset dystonia-parkinsonism disorder: Identification of a segregating mutation in the stress-response protein PRKRA. Lancet Neurol 7:207–215CrossRefPubMedGoogle Scholar
  15. 15.
    Paisan-Ruiz C, Bhatia KP, Li A et al (2009) Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Ann Neurol 65:19–23CrossRefPubMedGoogle Scholar
  16. 16.
    Bakowska JC, Wang H, Xin B et al (2008) Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism? Arch Neurol 65:520–524CrossRefPubMedGoogle Scholar
  17. 17.
    Patel H, Cross H, Proukakis C et al (2002) SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet 31:347–348PubMedGoogle Scholar
  18. 18.
    Windpassinger C, Wagner K, Petek E, Fischer R, Auer-Grumbach M (2003) Refinement of the ‘Silver syndrome locus’ on chromosome 11q12-q14 in four families and exclusion of eight candidate genes. Hum Genet 114:99–109CrossRefPubMedGoogle Scholar
  19. 19.
    Rainier S, Bui M, Mark E et al (2008) Neuropathy target esterase gene mutations cause motor neuron disease. Am J Hum Genet 82:780–785CrossRefPubMedGoogle Scholar
  20. 20.
    Hadano S, Nichol K, Brinkman RR et al (1999) A yeast artificial chromosome-based physical map of the juvenile amyotrophic lateral sclerosis (ALS2) critical region on human chromosome 2q33-q34. Genomics 55:106–112CrossRefPubMedGoogle Scholar

Copyright information

© US Government 2009

Authors and Affiliations

  • K. G. Meilleur
    • 1
    • 2
    • 3
    • 9
    • 10
  • M. Traoré
    • 4
  • M. Sangaré
    • 1
    • 4
  • A. Britton
    • 5
  • G. Landouré
    • 1
    • 4
    • 6
  • S. Coulibaly
    • 7
  • B. Niaré
    • 4
  • F. Mochel
    • 8
  • A. La Pean
    • 1
  • I. Rafferty
    • 5
  • C. Watts
    • 1
  • D. Shriner
    • 9
  • M. T. Littleton-Kearney
    • 3
  • C. Blackstone
    • 1
  • A. Singleton
    • 5
  • K. H. Fischbeck
    • 1
  1. 1.Neurogenetics Branch, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaUSA
  2. 2.National Institute of Nursing ResearchNational Institutes of HealthBethesdaUSA
  3. 3.School of NursingJohns Hopkins UniversityBaltimoreUSA
  4. 4.Department of NeurologyPoint G HospitalBamakoMali
  5. 5.National Institute of AgingNational Institutes of HealthBethesdaUSA
  6. 6.University College LondonLondonUK
  7. 7.Department of PsychiatryPoint G HospitalBamakoMali
  8. 8.INSERM U679Hôpital La SalpêtrièreParisFrance
  9. 9.Center for Research on Genomics and Global HealthNational Institutes of HealthBethesdaUSA
  10. 10.Center for Research on Genomics and Global HealthNational Human Genome Research InstituteBethesdaUSA

Personalised recommendations