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Human Genetics

, Volume 114, Issue 1, pp 99–109 | Cite as

Refinement of the "Silver syndrome locus" on chromosome 11q12-q14 in four families and exclusion of eight candidate genes

  • Christian Windpassinger
  • Klaus Wagner
  • Erwin Petek
  • Renate Fischer
  • Michaela Auer-GrumbachEmail author
Original Investigation

Abstract

Silver syndrome is a rare variant of autosomal dominant complicated hereditary spastic paraparesis (HSP), in which spasticity of the lower limbs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. The disease locus has been mapped to chromosome 11q12-q14. We report four Austrian families presenting with the typical clinical features of Silver syndrome. Sixteen individuals were affected upon clinical and/or electrophysiological examination. Ten persons showed mild to severe spasticity of the lower limbs. Wasting of the small hand muscles was present in nine affected family members of whom three had also gait disturbance. Three further individuals were asymptomatic. Electrophysiological studies showed normal or slightly to moderately slowed motor nerve conduction velocities, reduced amplitudes and occasionally chronodispersion of compound motor action potentials. In one patient, conduction block was observed. Sensory nerve action potentials were usually normal. Molecular genetic studies demonstrate linkage to chromosome 11q12-q14. Haplotype analysis in affected individuals indicates a common ancestor in the four families. By recombination analysis in affected individuals the Silver syndrome candidate gene interval can be reduced from 13 to 5.9 cM and can now be placed between the markers D11S1765 and D11S987. By sequence analysis of affected individuals eight functional and positional candidate genes could be excluded. Our study confirms the existence of the Silver syndrome locus on chromosome 11q12-q14 and provides the first report of nerve conduction velocity studies in Silver syndrome, which demonstrate the presence of a peripheral predominantly motor neuropathy.

Keywords

Tibial Nerve Motor Nerve Conduction Velocity Sensory Nerve Conduction Velocity Short Tandem Repeat Marker Functional Candidate Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors thank the family members for participation in this research project. We would also like to thank Mrs. A. Krenn and Mrs. A. Legenstein for their excellent technical assistance. This research project was supported by the Fonds zur Förderung der wissenschaftlichen Forschung (FWF P15378, Austria), the Tom-Wahlig-Stiftung Jena (TWS-FSP), Germany, the Muscular Dystrophy Association (MDA#3477), USA, and the Fachabteilung 6A—Wissenschaft und Forschung of the Styrian government

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Christian Windpassinger
    • 1
  • Klaus Wagner
    • 1
  • Erwin Petek
    • 1
  • Renate Fischer
    • 2
  • Michaela Auer-Grumbach
    • 1
    Email author
  1. 1.Institute of Medical Biology and Human GeneticsKarl-Franzens University GrazGrazAustria
  2. 2.Department of NeurologyKarl-Franzens UniversityGrazAustria

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