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. 2010 Sep;18(9):1065-7.
doi: 10.1038/ejhg.2010.68. Epub 2010 May 12.

A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42)

Nina A Schlipf  1 , Christian Beetz, Rebecca Schüle, Giovanni Stevanin, Anne Kjersti Erichsen, Sylvie Forlani, Cécile Zaros, Kathrin Karle, Stephan Klebe, Sven Klimpe, Alexandra Durr, Susanne Otto, Chantal M E Tallaksen, Olaf Riess, Alexis Brice, Peter Bauer, Ludger Schöls
Affiliations

A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42)

Nina A Schlipf et al. Eur J Hum Genet. 2010 Sep.

Abstract

The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. In this study, we screened 220 independent SPAST mutation-negative ADHSP samples for mutations in the SLC33A1 gene by high-resolution melting curve analysis. Conspicuous samples were validated by direct sequencing. Moreover, copy number variations affecting SLC33A1 were screened by multiplex ligation-dependent probe amplification assay. We could not identify potentially disease-causing mutations in our patients either by mutation scanning or by gene dosage analysis, as for the latter specific positive controls are not available to date. As our sample represents ADHSP patients for whom SPAST mutations and almost in all cases ATL1 and REEP1 mutations had been excluded, we consider SLC33A1 gene mutations as being very rare in a European ADHSP cohort, if present at all. To date, as SPG42 has still not been identified in a second, unrelated family, systematic genetic testing for SLC33A1 mutations is not recommended.

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Figures

Figure 1
Figure 1
Known SNP rs3804769 in SLC33A1. In total, 16 patients were found to be heterozygous for rs3804769 in SLC33A1 exon 1 (c.512A>G, p.D171G). A total of 16 variant alleles (7.0%) were present in 440 sample chromosomes, as assessed by high-resolution melting curve analysis (left part). Difference plot analysis revealed the heterozygous group (red), in addition to the homozygous samples (blue). Heterozygosity has been validated by conventional sequencing (right part).
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