Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome.
Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT-PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders.
Masellis
Mario
M
Linda C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre Toronto, Canada.
Momeni
Parastoo
P
Meschino
Wendy
W
Heffner
Reid
R
Elder
Joshua
J
Sato
Christine
C
Liang
Yan
Y
St George-Hyslop
Peter
P
Hardy
John
J
Bilbao
Juan
J
Black
Sandra
S
Rogaeva
Ekaterina
E
D001072:Apraxias / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D010375:Pedigree; D000077153:Progranulins; D022821:RNA Splice Sites / Q000235:genetics; D013577:Syndrome; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D022821:RNA Splice Sites