title: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity.
abstract: OBJECTIVE
  Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 (SPG11) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous.
  
  
  METHODS
  Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals.
  
  
  RESULTS
  Linkage was excluded in the four consanguineous families. In the only SPG11-linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene.
  
  
  CONCLUSIONS
  This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.
authors.affiliation: Laboratorio di Genetica Medica, Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Policlinico Sant'Orsola Malpighi, Università di Bologna, Bologna, Italy. tommaso.pippucci@unibo.it
authors.forename: T
authors.initials: T
authors.lastname: Pippucci
authors.forename: E
authors.initials: E
authors.lastname: Panza
authors.forename: E
authors.initials: E
authors.lastname: Pompilii
authors.forename: V
authors.initials: V
authors.lastname: Donadio
authors.forename: A
authors.initials: A
authors.lastname: Borreca
authors.forename: C
authors.initials: C
authors.lastname: Babalini
authors.forename: C
authors.initials: C
authors.lastname: Patrono
authors.forename: R
authors.initials: R
authors.lastname: Zuntini
authors.forename: T
authors.initials: T
authors.lastname: Kawarai
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: R
authors.initials: R
authors.lastname: Liguori
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
authors.forename: M
authors.initials: M
authors.lastname: Seri
mesh_terms: D000293:Adolescent; D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010375:Pedigree; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
chemical_list: D011506:Proteins; C520412:SPG11 protein, human