Unaffected mosaic C9orf72 case: RNA foci, dipeptide proteins, but upregulated C9orf72 expression.

ABSTRACT:

Objective

Suggested C9orf72 disease mechanisms for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration include C9orf72 haploinsufficiency, G₄C₂/C₄G₂ RNA foci, and dipeptide repeat (DPR) proteins translated from the G₄C₂ expansion; however, the role of small expansions (e.g., 30-90 repeats) is unknown and was investigated here.

Methods

We conducted a molecular and pathology study of a family in which the father (unaffected at age 90) carried a 70-repeat allele in blood DNA that expanded to ≈1,750 repeats in his children, causing ALS.

Results

Southern blotting revealed different degrees of mosaicism of small and large expansions in the father's tissues from the CNS. Sur

SUBMITTER: McGoldrick P 

PROVIDER: S-EPMC5798652 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature