Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.
BACKGROUND
Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses fail to detect exonic microdeletions.


METHODS
121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.


RESULTS
24 patients with 16 different heterozygotic exon deletions in SPG4 (20%) were identified, ranging from one exon to the whole coding sequence. Comparison with 78 patients with point mutations showed a similar clinical picture but an earlier age at onset.


CONCLUSIONS
Exon deletions in SPG4 are as frequent as point mutations, and SPG4 is responsible for 40% of AD-HSP.
Depienne
Christel
C
Fedirko
Estelle
E
Forlani
Sylvie
S
Cazeneuve
Cécile
C
Ribaï
Pascale
P
Feki
Imed
I
Tallaksen
Chantal
C
Nguyen
Karine
K
Stankoff
Bruno
B
Ruberg
Merle
M
Stevanin
Giovanni
G
Durr
Alexandra
A
Brice
Alexis
A
D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011174:Portugal / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology / Q000235:genetics*; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human