Characterization of a novel SPG3A deletion in a French-Canadian family.
Hereditary spastic paraplegias (HSPs) are characterized by progressive lower limb spasticity and weakness. Mutations in the SPG3A gene, which encodes the large guanosine triphosphatase atlastin, are the second most common cause of autosomal dominant hereditary spastic paraplegia. In a large SPG3A screen of 70 hereditary spastic paraplegia subjects, a novel in-frame deletion, p.del436N, was identified. Characterization of this deletion showed that it affects neither the guanosine triphosphatase activity of atlastin nor interactions between atlastin and spastin. Interestingly, immunoblot analysis of lymphoblasts from affected patients demonstrated a significant reduction in atlastin protein levels, supporting a loss-of-function disease mechanism.
Meijer
Inge A
IA
Center for the Study of Brain Diseases, Centre Hospitalier de l'Université de Montréal Research Center-Notre-Dame Hospital, University of Montreal, Québec, Canada.
Dion
Patrick
P
Laurent
Sandra
S
Dupré
Nicolas
N
Brais
Bernard
B
Levert
Annie
A
Puymirat
Jacques
J
Rioux
Marie France
MF
Sylvain
Michel
M
Zhu
Peng-Peng
PP
Soderblom
Cynthia
C
Stadler
Julia
J
Blackstone
Craig
C
Rouleau
Guy A
GA
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004568:Electrodiagnosis; D005190:Family; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000235:genetics*; D019204:GTP-Binding Proteins; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008565:Membrane Proteins; D008875:Middle Aged; D010264:Paraplegia / Q000175:diagnosis / Q000235:genetics*; D011792:Quebec; D012333:RNA, Messenger / Q000032:analysis; D017384:Sequence Deletion / Q000235:genetics*; D020798:Two-Hybrid System Techniques
D008565:Membrane Proteins; D012333:RNA, Messenger; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins