Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity

作者：Pippucci T^*; Panza E; Pompilii E; Donadio V; Borreca A; Babalini C; Patrono C; Zuntini R; Kawarai T; Bernardi G; Liguori R; Romeo G; Montagna P; Orlacchio A; Seri M

来源：European Journal of Neurology, 2009, 16(1): 121-126.

DOI：10.1111/j.1468-1331.2008.02367.x

• hereditary spastic paraplegia
• linkage analysis
• SPG11
• splice site mutations
• thinning of the corpus callosum

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.
Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals.
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.
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.

• 出版日期2009-1