BMC Neurology, Год журнала: 2024, Номер 24(1)
Опубликована: Сен. 17, 2024
Язык: Английский
European Journal of Neurology, Год журнала: 2025, Номер 32(1)
Опубликована: Янв. 1, 2025
Spinocerebellar ataxias (SCA) are neurodegenerative diseases with widespread lesions across the central nervous system. Ataxia and spasticity usually predominant, but patients may also present parkinsonism. We aimed to characterize substantia nigra pars compacta (SNc) degeneration in SCA2 7 using neuromelanin-sensitive imaging. Ataxic preataxic expansion carriers (n=15) SCA7 healthy controls (n=10) were prospectively recruited. Volume signal-to-noise ratio (SNR) values of SNc extracted from images. ROC curves used determine metrics that best differentiated SCA participants. Correlations between imaging measurements, clinical variables, plasma neurofilaments light chain (NfL) levels investigated. participants had lower SNR than (110.2 ± 1.3 versus 113.2 1.4; p < 0.001) those (112.5 2.1; 0.01). did not differ. In ataxic patients, volumes (0.13 0.04; = 0.06) (0.10 0.03, 0.02) compared (0.17 0.04). Signal decrease was detected at stage SCA2, SCA7. showed prominent involvement associative limbic nigral territories. discriminated (AUC ≥0.94). volume 1), ones. SCA7, correlations observed time onset, CAG repeats, severity scores, NfL. Neuromelanin-sensitive provides biomarkers SCAs, detectable which could potentially serve as outcome measures trials.
Язык: Английский
Процитировано
1
The Cerebellum, Год журнала: 2025, Номер 24(3)
Опубликована: Март 13, 2025
Язык: Английский
Процитировано
0
Genes, Год журнала: 2025, Номер 16(2), С. 216 - 216
Опубликована: Фев. 13, 2025
Fragile X, Huntington disease, and myotonic dystrophy type 1 are prototypical examples of human disorders caused by short tandem repeat variation, repetitive nucleotide stretches that highly mutable both in the germline somatic tissue. As repeats unstable, they can expand, contract, acquire lose epigenetic marks This means within an individual, genotype state at these loci vary considerably from cell to cell. mosaicism may play a key role clinical pathogenesis, yet, our understanding driving phenotypes is only just emerging. review focuses on three relatively well-studied where, given advent new technologies bioinformatic approaches, critical for coming into focus with respect cellular physiology phenotypes.
Язык: Английский
Процитировано
0
The Lancet Neurology, Год журнала: 2025, Номер 24(4), С. 282 - 284
Опубликована: Март 20, 2025
Язык: Английский
Процитировано
0
Human Genetics, Год журнала: 2024, Номер 143(11), С. 1363 - 1378
Опубликована: Окт. 8, 2024
Abstract Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is caused by the expansion of a genetically unstable polyglutamine-encoding CAG repeat in ATXN3 . Longer alleles are generally associated with earlier onset and frequent intergenerational expansions mediate anticipation observed this disorder. Somatic has also been implicated slowing rate somatic proposed as therapeutic strategy. Here, we utilised high-throughput ultra-deep MiSeq amplicon sequencing to precisely define number sequence repeat, genotype an adjacent single nucleotide variant quantify blood buccal swab DNA cohort individuals SCA3 from Azores islands (Portugal). We revealed systematic mis-sizing high levels inaccuracy traditional fragment length analysis that have important implications for attempts identify modifiers clinical molecular phenotypes. Quantification multivariate regression expected effects age at sampling length, although effect was surprisingly modest much stronger associations age. association downstream rs12895357 expansion, higher level compared blood. These data suggest locus patients or might serve good biomarker trials testing suppressors peripheral exposure.
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 26, 2024
Abstract Expansions and contractions of tandem DNA repeats are a source genetic variation in human populations tissues: some expanded cause inherited disorders, also somatically unstable. We analyzed sequence data, derived from the blood cells >700,000 participants UK Biobank All Us Research Program, developed new computational approaches to recognize, measure learn DNA-repeat instability at 15 highly polymorphic CAG-repeat loci. found that expansion contraction rates varied widely across these loci, even for alleles same length; different loci exhibited variable relative propensities mutate germline versus blood. The high somatic TCF4 enabled genome-wide association analysis identified seven which variants modulate repeat cells. Three implicated contained genes ( MSH3 , FAN1 PMS2 ) Huntington’s disease age-at-onset as well HTT blood; however, specific their effects (instability-increasing or-decreasing) appeared be tissue-specific repeat-specific, suggesting mutation tissues—or tissue—proceeds independently under control substantially variation. Additional modifier included damage response ATAD5 GADD45A . Analyzing expansions together with clinical data showed 5’ UTR glutaminase GLS) gene associated stage 5 chronic kidney (OR=14.0 [5.7–34.3]) liver diseases (OR=3.0 [1.5–5.9]). These other results point dynamics lifespan.
Язык: Английский
Процитировано
1
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июль 3, 2024
Spinocerebellar ataxia 27B (SCA27B) is a common autosomal dominant caused by an intronic GAA•TTC repeat expansion in
Язык: Английский
Процитировано
0
BMC Neurology, Год журнала: 2024, Номер 24(1)
Опубликована: Сен. 17, 2024
Язык: Английский
Процитировано
0