ArticleEuropean journal of human genetics : EJHG2024
Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype.
Article in European journal of human genetics : EJHG, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- The clinical phenotype of carriers of intermediate alleles in the huntingtin gene: A scoping review.Journal of Huntington's disease · 2026Review
- The HTT gene influences plasma neurofilament light chain and brain metabolism in prodromal Alzheimer's disease.Journal of neurology · 2025Article
- AI-Enhanced Transcriptomic Discovery of Druggable Targets and Repurposed Therapies for Huntington's Disease.Brain sciences · 2025Review
- Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.bioRxiv : the preprint server for biology · 2025Article
- Optical genome mapping enables accurate testing of large repeat expansions.Genome research · 2025Article
- Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.Journal of Huntington's disease · 2025Article
- Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles ofBrain communications · 2025Article
- Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Hitting the heights with CiteScore.European journal of human genetics : EJHG · 2024Article
- Comment on: "Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype" by Ruiz de Sabando et al.European journal of human genetics : EJHG · 2024Article
- Huntington's Disease and Dentistry: A Review of Its Etiology, Clinical Presentation, Symptomatic Pharmacotherapy, and Dental Management.Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryReview
Corrections and comments
- Commented on by
Authors and funding
7 authors at 11 institutions in 2 countries.
Funding
Abstract
Huntington disease (HD) is a neurodegenerative disorder caused by ≥36 CAGs in the HTT gene. Intermediate alleles (IAs) (27-35 CAGs) are not considered HD-causing, but their potential association with neurocognitive symptoms remains controversial. As HTT somatic CAG expansion influences HD onset, we hypothesised that IAs are somatically unstable, and that somatic CAG expansion may drive phenotypic presentation in some IA carriers. We quantified HTT somatic CAG expansions by MiSeq sequencing in the blood DNA of 164 HD subjects and 191 IA (symptomatic and control) carriers, and in the brain DNA of a symptomatic 33 CAG carrier. We also performed genotype-phenotype analysis. The phenotype of symptomatic IA carriers was characterised by motor (85%), cognitive (27%) and/or behavioural (29%) signs, with a late (58.7 ± 18.6 years), but not CAG-dependent, age at onset. IAs displayed somatic expansion that were CAG and age-dependent in blood DNA, with 0.4% and 0.01% of DNA molecules expanding by CAG and year, respectively. Somatic expansions of +1 and +2 CAGs were detected in the brain of the individual with 33 CAGs, with the highest expansion frequency in the putamen (10.3%) and the lowest in the cerebellum (4.8%). Somatic expansion in blood DNA was not different in symptomatic vs. control IA carriers. In conclusion, we show that HTT IAs are somatically unstable, but we found no association with HD-like phenotypes. It is plausible, however, that some IAs, close to the HD pathological threshold and with a predisposing genetic background, could manifest with neurocognitive symptoms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.