title: Refinement of the SPG9 locus on chromosome 10q23.3-24.2 and exclusion of candidate genes.
abstract: OBJECTIVE
  The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders, characterized by a progressive spasticity of the lower limbs. So far, 33 different loci (SPGs) have been mapped and the 15 genes responsible have been identified. We mapped a locus responsible for a form of spastic paraplegia, complicated by bilateral cataracts, gastroesophageal reflux with persisting vomiting and amyotrophy to chromosome 10q23.3-q24.2, in an Italian family. The critical region was in a 12 cm chromosomal interval between markers D10S564 and D10S603 (SPG9, MIM601162). In the same region, two other forms of HSP have been recently mapped: SPG27 and SPG33. In the latter case, the gene responsible has been identified.
  
  
  METHODS
  To better characterize this region, we genotyped individuals from SPG9-linked families using additional markers and reduced the candidate region to a 4.8 Mb, excluding several genes by positional cloning.
  
  
  RESULTS
  The refined SPG9 locus is positioned completely within SPG27 and does not include the SPG33 gene.
  
  
  CONCLUSIONS
  Fifty-two transcripts are present in the refined critical region and 25 strong candidates have been excluded as disease causing genes by direct sequencing. Six of them were also excluded as responsible for SPG27.
authors.affiliation: Laboratory of Medical Genetics, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy. emanuele.panza2@.unibo.it
authors.forename: E
authors.initials: E
authors.lastname: Panza
authors.forename: T
authors.initials: T
authors.lastname: Pippucci
authors.forename: R
authors.initials: R
authors.lastname: Cusano
authors.forename: C
authors.initials: C
authors.lastname: Lo Nigro
authors.forename: L
authors.initials: L
authors.lastname: Pradella
authors.forename: S
authors.initials: S
authors.lastname: Contardi
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: G
authors.initials: G
authors.lastname: Stevanin
authors.forename: R
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: R
authors.initials: R
authors.lastname: Liguori
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: M
authors.initials: M
authors.lastname: Seri
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D009154:Mutation; D020161:Physical Chromosome Mapping / Q000379:methods*; D017422:Sequence Analysis, DNA; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*