Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity.
Induced pluripotent stem cells (iPSCs) were generated from peripheral blood-derived erythroid progenitor cells obtained from a presymptomatic female carrying the heterozygous R418Xprogranulin (GRN) nonsense mutation, known to cause autosomal dominant frontotemporal lobar degeneration.
Heterozygous loss-of-function mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A).
Suppression of Progranulin Expression Leads to Formation of Intranuclear TDP-43 Inclusions In Vitro: A Cell Model of Frontotemporal Lobar Degeneration.
We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy.
In several types of cancers, progranulin expression is upregulated, whereas function-interfering mutations in the granulin gene in humans have been linked to a subset of heritable cases of frontotemporal lobar degeneration.
Loss-of-function mutations in progranulin (GRN) and a non-coding (GGGGCC)<sub>n</sub> hexanucleotide repeat expansions in C9ORF72 are the two most common genetic causes of frontotemporal lobar degeneration with aggregates of TAR DNA binding protein 43 (FTLD-TDP).
Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP).
Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia.
All seven participants with available brain autopsies (6 GRN+/A152T+, 1 GRN+/A152T-) showed frontotemporal lobar degeneration with TDP-43 inclusions (type A classification), which is characteristic of GRN carriers.
However, how progranulin and TMEM106B interact to regulate lysosomal function and frontotemporal lobar degeneration (FTLD) disease progression is still unclear.
Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease.
Heterozygous loss-of-function mutations in GRN, the progranulin gene, which result in progranulin (PGRN) protein haploinsufficiency, are a major cause of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).
Here, we present a novel GRN mutation resulting in frontotemporal lobar degeneration with a distinct clinical phenotype, and we review reports of GRN mutations associated with familial phenotypic heterogeneity.
Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis.