Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity |
| |
Authors: | T Pippucci E Panza E Pompilii V Donadio A Borreca C Babalini C Patrono R Zuntini T Kawarai G Bernardi R Liguori G Romeo P Montagna A Orlacchio M Seri |
| |
Institution: | Laboratorio di Genetica Medica, Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Policlinico Sant'Orsola Malpighi, Universitàdi Bologna, Bologna, Italy;;Dipartimento di Scienze Neurologiche, Universitàdi Bologna, Bologna, Italy;;CERC-IRCCS Santa Lucia, Laboratorio di Neurogenetica, Rome, Italy;;Dipartimento di Neuroscienze, Universitàdi Roma "Tor Vergata", Rome, Italy;;and Hyogo Brain and Heart Center, Department of Neurology, Himeji city, Japan |
| |
Abstract: | Background and purpose: 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. Discussion: 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. |
| |
Keywords: | hereditary spastic paraplegia linkage analysis SPG11 splice site mutations thinning of the corpus callosum |
|
|