title: Progranulin mutation analysis: Identification of one novel mutation in exon 12 associated with frontotemporal dementia.
abstract: 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.
authors.affiliation: Cognition & Behavioral Neurology Section, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India.
authors.forename: Peethambaran Mallika
authors.initials: PM
authors.lastname: Aswathy
authors.affiliation: Cognition & Behavioral Neurology Section, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India.
authors.forename: Pushparajan Sulajamani
authors.initials: PS
authors.lastname: Jairani
authors.affiliation: Cognition & Behavioral Neurology Section, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India.
authors.forename: Sheela Kumari
authors.initials: SK
authors.lastname: Raghavan
authors.affiliation: Integrated Divisions of Cognitive & Motor Aging (Neurology) and Geriatrics (Medicine), Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Verghese
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Gopala
authors.affiliation: Cancer Research Program-5, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Srinivas
authors.affiliation: Cognition & Behavioral Neurology Section, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India; Department of Neurology, National Institute of Mental Health & Neuro Sciences (NIMHANS), Bangalore, India. Electronic address: psmathu@yahoo.com.
authors.forename: Pavagada Sivasankara
authors.initials: PS
authors.lastname: Mathuranath
mesh_terms: D000368:Aged; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger
keywords: Frontotemporal dementia; Nonsense-mediated decay; Null mutation; PGRN; Progranulin