Movement Disorders Clinical Practice, Год журнала: 2023, Номер 10(11), С. 1597 - 1598
Опубликована: Авг. 31, 2023
Язык: Английский
Movement Disorders, Год журнала: 2024, Номер 39(3), С. 486 - 497
Опубликована: Янв. 10, 2024
Abstract Background Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant with invariable sensory neuropathy originally described in a family Swedish ancestry residing Utah more than 25 years ago. Despite tight linkage to the 16q22 region, molecular diagnosis has since remained elusive. Objectives Inspired by pathogenic structural variation implicated other 16q‐ataxias same locus, we revisited index SCA4 cases from using novel technologies investigate within candidate region. Methods We adopted targeted long‐read sequencing approach adaptive sampling on Oxford Nanopore Technologies (ONT) platform that enables detection of segregating variants genomic region without priori assumptions about any variant features. Results Using this approach, found heterozygous (GGC) n repeat expansion last coding exon zinc finger homeobox 3 ( ZFHX3 ) gene segregates disease, ranging between 48 and 57 GGC repeats affected probands. This finding was replicated separate SCA4. Furthermore, estimation size short‐read whole genome (WGS) data 21,836 individuals recruited 100,000 Genomes Project UK our in‐house dataset 11,258 exomes did not reveal repeats, indicating ultrarare. Conclusions These findings support utility as powerful tool decipher causative unsolved inherited neurological disease. © 2024 The Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.
Язык: Английский
Процитировано
30
EBioMedicine, Год журнала: 2024, Номер 102, С. 105077 - 105077
Опубликована: Март 21, 2024
BackgroundAn intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile ataxia large Chinese cohort.MethodsA total 1216 patients that included 399 typical late-onset cerebellar (LOCA), 290 early-onset (EOCA), 527 multiple system atrophy with predominant (MSA-c) were enrolled. Long-range repeat-primed PCR performed screen for expansions FGF14. Targeted long-read whole-genome sequencing determine size sequence configuration. A multi-modal study including clinical assessment, MRI, neurofilament light chain conducted disease assessment.Findings17 positive (GAA)≥250 (12 GAA-pure expansion, five (GAA)≥250-[(GAA)n (GCA)m]z expansion) two possible biallelic (GAA)202/222 alleles identified. The phenotypes 19 cases covered LOCA phenotype, EOCA phenotype MSA-c phenotype. Five six found have another genetic disorder. NfL levels significantly higher than age-matched controls (p < 0.001). pre-ataxic individuals lower SCA3 0.001) similar controls.InterpretationThe cohort low (1.3%). Biallelic co-occurrence other acquired or hereditary diseases may contribute variation different progression.FundingThis funded by National Key R&D Program China (2021YFA0805200 H.J.), Natural Science Foundation (81974176 82171254 H.J.; 82371272 Z.C.; 82301628 L.W.; 82301438 Z.L.; 82201411 L.H.), Innovation Research Group Project Hunan Province (2020JJ1008 Development (2020SK2064 Innovative Reform Commission H.J., (2024JJ3050 2022JJ20094 2021JJ40974 2022JJ40783 L.H.; 2022JJ40703 Z.L.), Clinical Center Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 Central South University Programme Advanced Interdisciplinary Study (2023QYJC010 H.J.) Technology (2022RC1027 Z.C.). D.P. holds Fellowship award from Canadian Institutes Health (CIHR).
Язык: Английский
Процитировано
18
Current Neurology and Neuroscience Reports, Год журнала: 2025, Номер 25(1)
Опубликована: Янв. 16, 2025
Язык: Английский
Процитировано
1
Movement Disorders, Год журнала: 2025, Номер unknown
Опубликована: Янв. 24, 2025
Abstract Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome‐wide analyses can reveal novel genotype–phenotype associations and provide a diagnosis for patients families. Objective The aim was to identify the cause severe progressive disorder phenotype in 2 affected brothers. Methods A family brothers unaffected parents had extensive phenotyping since birth. Whole‐genome long‐read sequencing methods characterized methylation status. Results Two male siblings CGG expansion 5′‐untranslated region (UTR) disco‐interacting protein homolog B ( DIP2B ) presented phenotype, including neurodevelopmental disability, dysmorphic traits, (chorea, dystonia, ataxia). Conclusions This is first report 5′‐UTR. © 2025 International Parkinson Movement Disorder Society. article has been contributed by U.S. Government employees their work public domain USA.
Язык: Английский
Процитировано
0
The Cerebellum, Год журнала: 2025, Номер 24(3)
Опубликована: Апрель 8, 2025
Язык: Английский
Процитировано
0
New England Journal of Medicine, Год журнала: 2023, Номер 388(21)
Опубликована: Май 24, 2023
Процитировано
10
BMJ Open, Год журнала: 2024, Номер 14(9), С. e084865 - e084865
Опубликована: Сен. 1, 2024
This study aims to assess the patient-reported benefits and costs of coordinated care multidisciplinary at specialist ataxia centres (SACs) in UK compared with delivered standard neurological clinics.
Язык: Английский
Процитировано
2
Human Genetics and Genomics Advances, Год журнала: 2024, Номер 6(1), С. 100372 - 100372
Опубликована: Окт. 17, 2024
Язык: Английский
Процитировано
1
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 5, 2024
Abstract Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with several movement disorders. Unbiased genome-wide analyses can reveal novel genotype-phenotype associations and provide a diagnosis for patients families. Objectives To identify the cause severe progressive disorder phenotype in two affected brothers. Methods A family brothers unaffected parents had extensive phenotyping natural history followed since birth. Whole-genome long-read sequencing methods were used to characterize methylation status. Results: We describe CGG expansion 5’-untranslated region DIP2B male siblings presenting including neurodevelopmental disability, dysmorphic traits, (prominent chorea, dystonia, ataxia). Conclusions This is first report attributed 5’-UTR.
Язык: Английский
Процитировано
0
Movement Disorders, Год журнала: 2024, Номер unknown
Опубликована: Дек. 9, 2024
Abstract Background A CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia two Chinese families. Expanded repeats ranged from 45 100 units, CAA sequence interruptions the 5′ region and an uninterrupted tract 3′ tail. Objective Here, we assess population distribution of repeat, its contribution neurological diseases. Methods We interrogated data 54,788 individuals Genomics England, 10,686 patients UCL Queen Square Institute Neurology in‐house database (UCL IoN), 424,340 UK Biobank. Results identified expanded four learning difficulties without three Biobank, one hereditary ataxia, neuropathy, neurodegenerative disease. showed a linear relationship between number overall length. Conclusions These results indicate that expansions are rare British structures predisposed may more common non‐British ancestries. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society.
Язык: Английский
Процитировано
0