title: A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42).
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.
authors.affiliation: Department of Medical Genetics, Institute of Human Genetics, Tübingen, Germany.
authors.forename: Nina A
authors.initials: NA
authors.lastname: Schlipf
authors.forename: Christian
authors.initials: C
authors.lastname: Beetz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schüle
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Anne Kjersti
authors.initials: AK
authors.lastname: Erichsen
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Cécile
authors.initials: C
authors.lastname: Zaros
authors.forename: Kathrin
authors.initials: K
authors.lastname: Karle
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.forename: Sven
authors.initials: S
authors.lastname: Klimpe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Susanne
authors.initials: S
authors.lastname: Otto
authors.forename: Chantal M E
authors.initials: CM
authors.lastname: Tallaksen
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
mesh_terms: D005799:Genes, Dominant; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010264:Paraplegia / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; C484549:SLC33A1 protein, human
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