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