Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles of <i>HTT</i> associated with an early disease onset in <i>C9orf72</i> carriers.

ABSTRACT: Carriers of the GGGGCC pathogenic expansion in C9orf72 can develop symptoms of frontotemporal dementia and/or amyotrophic lateral sclerosis, with variable and unpredictable ages at onset. Previous studies aiming to decipher the genetic bases of the clinical variability in this rare disease included bi-allelic polymorphisms, excluding short tandem repeats. Whole-genome sequencing data of 195 C9orf72 patients were used to consider all short tandem repeats linked to polyglutamine disorders as potential genetic modifiers given the existing links between C9orf72 and polyglutamine diseases. Intermediate alleles of HTT encoding huntingtin were associated with an earlier age at onset among C9orf72 carriers in the discovery cohort (n = 195, P = 0.000

SUBMITTER: Barbier M 

PROVIDER: S-EPMC12204198 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature