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

Authors: Pippucci, T.¹; Panza, E.¹; Pompilii, E.¹; Donadio, V.²; Borreca, A.; Babalini, C.³; Patrono, C.³; Zuntini, R.¹; Kawarai, T.⁴; Bernardi, G.; Liguori, R.²; Romeo, G.¹; Montagna, P.²; Orlacchio, A.; Seri, M.¹

Source: European Journal of Neurology, Volume 16, Number 1, January 2009 , pp. 121-126(6)

Publisher: Wiley-Blackwell

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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

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1468-1331.2008.02367.x

Affiliations: 1: Laboratorio di Genetica Medica, Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Policlinico Sant'Orsola Malpighi, Università di Bologna, Bologna, Italy 2: Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna, Italy 3: CERC-IRCCS Santa Lucia, Laboratorio di Neurogenetica, Rome, Italy 4: Hyogo Brain and Heart Center, Department of Neurology, Himeji city, Japan

Publication date: 2009-01-01

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

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