TY - JOUR
T1 - Autosomal recessive hereditary spastic paraplegia with thin corpus callosum
T2 - A novel mutation in the SPG11 gene and further evidence for genetic heterogeneity
AU - Pippucci, T.
AU - Panza, E.
AU - Pompilii, E.
AU - Donadio, V.
AU - Borreca, A.
AU - Babalini, C.
AU - Patrono, C.
AU - Zuntini, R.
AU - Kawarai, T.
AU - Bernardi, G.
AU - Liguori, R.
AU - Romeo, G.
AU - Montagna, P.
AU - Orlacchio, A.
AU - Seri, M.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Hereditary spastic paraplegia
KW - Linkage analysis
KW - SPG11
KW - Splice site mutations
KW - Thinning of the corpus callosum
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U2 - 10.1111/j.1468-1331.2008.02367.x
DO - 10.1111/j.1468-1331.2008.02367.x
M3 - Article
C2 - 19087158
AN - SCOPUS:57449117098
VL - 16
SP - 121
EP - 126
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
IS - 1
ER -