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

Nina A Schlipf, 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
Eur J Hum Genet. 2010-05-12; 18(9): 1065-1067
DOI: 10.1038/ejhg.2010.68

Lire sur PubMed

1. Eur J Hum Genet. 2010 Sep;18(9):1065-7. doi: 10.1038/ejhg.2010.68. Epub 2010 May

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

Schlipf NA(1), Beetz C, Schüle R, Stevanin G, Erichsen AK, Forlani S, Zaros C,
Karle K, Klebe S, Klimpe S, Durr A, Otto S, Tallaksen CM, Riess O, Brice A, Bauer
P, Schöls L.

Author information:
(1)Department of Medical Genetics, Institute of Human Genetics, Tübingen,

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

DOI: 10.1038/ejhg.2010.68
PMCID: PMC2987419
PMID: 20461110 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus