Screening for the hereditary spastic paraplaegias SPG4 and SPG3A with the multiplex ligation-dependent probe amplification technique in a large population of affected individuals.
Hereditary spastic paraplaegias are a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. The most common forms of hereditary spastic paraplaegia are SPG4 and SPG3A caused by sequence variants in the SPAST and ATL1 genes, as well as by deletions and duplications not detected by standard techniques. In this study, we used the multiplex ligation-dependent probe amplification (MLPA) analysis for screening 93 patients (52 familial and 41 isolated cases). As a result, we identified 11 different deletions and 1 duplication in the SPAST gene and a single exon deletion in the ATL1 gene. These results indicate that micro-rearrangements in the SPAST gene are a fairly frequent cause of hereditary spastic paraplaegia and that MLPA is a useful and efficient technique to detect a considerable proportion of the mutations in the most common forms of hereditary spastic paraplaegias.
Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland. suleka@ipin.edu.pl
Anna
A
Sulek
Ewelina
E
Elert
Marta
M
Rajkiewicz
Elzbieta
E
Zdzienicka
Iwona
I
Stepniak
Wioletta
W
Krysa
Jacek
J
Zaremba
D000251:Adenosine Triphosphatases / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D017384:Sequence Deletion; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics; D000074181:Spastin
D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human