TY - JOUR
T1 - Progranulin mutation analysis
T2 - Identification of one novel mutation in exon 12 associated with frontotemporal dementia
AU - Aswathy, Peethambaran Mallika
AU - Jairani, Pushparajan Sulajamani
AU - Raghavan, Sheela Kumari
AU - Verghese, Joe
AU - Gopala, Srinivas
AU - Srinivas, Priya
AU - Mathuranath, Pavagada Sivasankara
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a familial behavioral variant FTD patient (accounting for ~1% of total FTD cases and 6% of familial FTD cases). This mutation was found to introduce a premature termination codon and the prematurely terminated messenger RNA may probably undergo nonsense-mediated decay. In enzyme-linked immunosorbent assay, the proband showed significantly reduced level of plasma PGRN (28 ng/mL) compared with controls (150 ± 38 ng/mL), which implicates haploinsufficiency as the pathogenic mechanism.
AB - Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a familial behavioral variant FTD patient (accounting for ~1% of total FTD cases and 6% of familial FTD cases). This mutation was found to introduce a premature termination codon and the prematurely terminated messenger RNA may probably undergo nonsense-mediated decay. In enzyme-linked immunosorbent assay, the proband showed significantly reduced level of plasma PGRN (28 ng/mL) compared with controls (150 ± 38 ng/mL), which implicates haploinsufficiency as the pathogenic mechanism.
KW - Frontotemporal dementia
KW - Nonsense-mediated decay
KW - Null mutation
KW - PGRN
KW - Progranulin
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U2 - 10.1016/j.neurobiolaging.2015.11.026
DO - 10.1016/j.neurobiolaging.2015.11.026
M3 - Article
C2 - 26724960
AN - SCOPUS:85014543400
SN - 0197-4580
VL - 39
SP - 218.e1-218.e3
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -