Incidentalome

Gene: TARDBP

Green List (high evidence)

Well established gene with >5 cases presenting with TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia.

PMID: 18309045 – In vivo functional assay: Tagged wildtype TDP43 cells with mutated (Q331K and M337V) TDP43 cells in the spinal cords of Hamburger Hamilton stage 14 chick embryos. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) staining showed that there was a dramatic reduction in maturation leading to developmental failure of limb and tail buds. Findings suggested a toxic gain of function or dominant negative effect of mutant TDP43.

PMID 18309045: A missense variant (M337V) was identified in 4 affected individuals from a family of English descent. The variant was shown to segregate across two generations.

PMID: 19609911: Hungarian individual identified with a missense mutation (K263E) in exon 6 (known to be a glycine reach critical domain) who is known to have frontotemporal lobar degeneration.

Created: 5 Apr 2023, 4:21 a.m. | Last Modified: 5 Apr 2023, 4:21 a.m.

Panel Version: 0.229

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis 10, with or without FTD; Frontotemporal lobar degeneration, TARDBP-related (MIM#612069; MONDO: 0012790)

Publications

• 18309045
• 19609911

Mode of pathogenicity
Other