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

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

1 Institute of Human Genetics

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

Mots clés: hereditary spastic paraplegia; SLC33A1; SPG42

Peter Bauer, Nina Schlipf, Christian Beetz, Rebecca Schüle, Giovanni Stevanin, et al.. 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1-gene (SPG42). European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.68⟩. ⟨hal-00535578⟩