The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype - PubMed (original) (raw)

The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype

H Patel et al. Am J Hum Genet. 2001 Jul.

Abstract

The hereditary spastic paraplegias (HSPs) are a complex group of neurodegenerative disorders characterized by lower-limb spasticity and weakness. Silver syndrome (SS) is a particularly disabling dominantly inherited form of HSP, complicated by amyotrophy of the hand muscles. Having excluded the multiple known HSP loci, we undertook a genomewide screen for linkage of SS in one large multigenerational family, which revealed evidence for linkage of the SS locus, which we have designated "SPG17," to chromosome 11q12-q14. Haplotype construction and analysis of recombination events permitted the minimal interval defining SPG17 to be refined to approximately 13 cM, flanked by markers D11S1765 and D11S4136. SS in a second family was not linked to SPG17, demonstrating further genetic heterogeneity in HSP, even within this clinically distinct subtype.

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Figures

Figure 1

Structure of SS pedigrees 1 and 2. Blackened symbols denote affected individuals.

Figure 2

Chromosome 11q12-q14 haplotype. The haplotype segregating with SS is in black. Reconstructed genotypes are in parentheses. Recombination events in affected individuals restrict the critical interval to an ∼13-cM region between D11S1765 and D11S4136. Blackened symbols denote affected individuals.

Figure 3

Haplotype for pedigree 2, showing microsatellites in the region that shows linkage of SS in family 1. Blackened symbols denote affected individuals.

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References

Electronic-Database Information

1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/ (for microsatellite-marker map)
1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for SS [MIM 270685])

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The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype - PubMed (original) (raw)