A novel GRN mutation (GRN c.708+6_+9delTGAG) in frontotemporal lobar degeneration with TDP-43-positive inclusions: clinicopathologic report of 6 cases.
Understanding of frontotemporal lobar degeneration, the underlying pathology most often linked to the clinical diagnosis of frontotemporal dementia, is rapidly increasing. Mutations in 7 known genes (MAPT, GRN, C9orf72, VCP, CHMP2B, and, rarely, TARDBP and FUS) are associated with frontotemporal dementia, and the pathologic classification of frontotemporal lobar degeneration has recently been modified to reflect these discoveries. Mutations in one of these genes (GRN), which encodes progranulin, have been implicated in up to a quarter of cases of frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 43)-positive inclusions; currently, there are more than 60 known pathogenic mutations of the gene. We present the clinical, pathologic, and genetic findings on 6 cases from 4 families, 5 of which were shown to have a novel GRN c.708+6_+9delTGAG mutation.
From the Departments of Pathology (ENB-I, EHB), Psychiatry and Behavioral Science (SW), and Neurology (MM), Northwestern University; Northwestern Cognitive Neurology and Alzheimer Disease Center (SW, MM, EHB); and Rush University Medical Center (JAS), Chicago, Illinois; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (ES, SEA, EM-W, VMVD, JQT); Department of Neurology, University of Iowa, Iowa City, Iowa (H-SS); Massachusetts General Hospital, Boston, Massachusetts (BTH, MPF); and Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida (MCB, RR).
Esther N
EN
Bit-Ivan
Eunran
E
Suh
Hyung-Sub
HS
Shim
Sandra
S
Weintraub
Bradley T
BT
Hyman
Steven E
SE
Arnold
Elisabeth
E
McCarty-Wood
Viviana M
VM
Van Deerlin
Julie A
JA
Schneider
John Q
JQ
Trojanowski
Matthew P
MP
Frosch
Matt C
MC
Baker
Rosa
R
Rademakers
Marsel
M
Mesulam
Eileen H
EH
Bigio
D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins
D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins