Propensity for somatic expansion increases over the course of life in Huntington disease - Sorbonne Université
Journal Articles eLife Year : 2021

Propensity for somatic expansion increases over the course of life in Huntington disease

Abstract

Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease.
Fichier principal
Vignette du fichier
elife-64674-v1.pdf (5.99 Mo) Télécharger le fichier
Origin Publication funded by an institution

Dates and versions

hal-03230958 , version 1 (20-05-2021)

Identifiers

Cite

Radhia Kacher, François-Xavier Lejeune, Sandrine Noël, Cécile Cazeneuve, Alexis Brice, et al.. Propensity for somatic expansion increases over the course of life in Huntington disease. eLife, 2021, 10, pp.e64674. ⟨10.7554/eLife.64674⟩. ⟨hal-03230958⟩
36 View
59 Download

Altmetric

Share

More