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

Hum Genet. 2007 Nov;122(3-4):261-73. doi: 10.1007/s00439-007-0396-1. Epub 2007 Jun 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 8 / genetics*
  • Female
  • Genes, Dominant*
  • Genetic Markers
  • Haplotypes
  • Humans
  • Kinesins / genetics
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Neuregulin-1
  • Pedigree
  • Spastic Paraplegia, Hereditary / genetics*


  • Genetic Markers
  • NRG1 protein, human
  • Nerve Tissue Proteins
  • Neuregulin-1
  • KIF13B protein, human
  • Kinesins