title: Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration.
abstract: Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease with an age at onset generally below 65 years. Mutations in progranulin (GRN) have been reported to be able to cause FTLD through haploinsufficiency. We have sequenced GRN in 121 patients with FTLD and detected six different mutations in eight patients: p.Gly35Glufs*19, p.Asn118Phefs*4, p.Val200Glyfs*18, p.Tyr294*, p.Cys404* and p.Cys416Leufs*30. Serum was available for five of the mutations, where the serum-GRN levels were found to be >50% reduced compared with FTLD patients without GRN mutations. Moreover, the p.Cys416Leufs*30 mutation segregated in an affected family with different dementia diagnoses. The mutation frequency of GRN mutation was 6.6% in our FTLD cohort.
authors: Department of NVS, Karolinska Institutet, KI-Alzheimer Disease Research Center, Stockholm, Sweden.
authors: Huei-Hsin
authors: HH
authors: Chiang
authors: Charlotte
authors: C
authors: Forsell
authors: Lena
authors: L
authors: Lilius
authors: Linn
authors: L
authors: Öijerstedt
authors: Steinunn
authors: S
authors: Thordardottir
authors: Krishnan
authors: K
authors: Shanmugarajan
authors: Marie
authors: M
authors: Westerlund
authors: Inger
authors: I
authors: Nennesmo
authors: Håkan
authors: H
authors: Thonberg
authors: Caroline
authors: C
authors: Graff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism; D005190:Family; D057174:Frontotemporal Lobar Degeneration / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000077153:Progranulins
chemical_list: D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins