The Lancet regional health. Europe · 2026
Whole genome sequencing in cerebral palsy: a UK paediatric pilot study.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ratnaike Thiloka E, Pierce Heather H, Coffey Alison J, Dias Joao M L, Kean Iain R L, Li Emily, More Ravi P, Sumathipala Dulika S, Bajracharya Maya, Kingsbury Zoya, Newington Taksina, Rogers Anthony S, Delon Isabelle, Downes Kate, de Alwis Yasmin, Basu Anna P, Issa Manal, Kearney Catherine, Khan Amjad H, Marlow Benjamin P, Sansome Alison, Ahn JooWook, Than A Yee, Lau Tracy, Bentley David R, Bowdin Sarah, Reid Evan, Houlden Henry, Humphray Sean, Rowitch David H
Аннотация
BACKGROUND: Prior international studies indicate that 9-36% of people with cerebral palsy (CP) have a monogenic condition. However, the utility of whole genome sequencing (WGS) as a diagnostic tool for United Kingdom (UK) National Health Service (NHS) patients has not been evaluated.
METHODS: This prospective pilot study recruited 86 individuals with CP from specialist clinics in Bedford, Cambridge, Colchester, Newcastle, and Luton NHS Foundation Trusts. Gene-agnostic trio WGS was performed using AI-based variant prioritisation, with subsequent application of a CP gene list. Candidate diagnostic pathogenic (P) or likely pathogenic (LP) variants were reviewed at multidisciplinary meetings and confirmed in an NHS Genomic Laboratory Hub prior to issuing a clinical report. The use of human phenotype ontology (HPO) terms was evaluated to estimate probability of a diagnostic variant using a supervised linear discriminant analysis (PCA + LDA) model.
FINDINGS: 86/157 (54.7%) individuals approached consented to the study. Variants meeting P/LP diagnostic criteria were identified in 11/86 cases (12.8%). 8/86 participants (9.3%) carried variants strongly suggestive of disease causation. Variants of uncertain significance were identified in 27/86 cases (31.4%). In all cases with P/LP variants, findings informed patient prognosis, specialist care, clinical management, and familial recurrence risk. Machine learning approaches were used to segregate the probability of diagnosis for participants based on HPO terms.
INTERPRETATION: WGS is clinically useful for diagnosis and management of genetic conditions associated with CP in the UK. Validation of these findings in a larger cohort is warranted.
FUNDING: Rosetrees Charitable Trust, Isaac Newton Trust, NIHR Cambridge Biomedical Research Centre, and the Wellcome Trust.
METHODS: This prospective pilot study recruited 86 individuals with CP from specialist clinics in Bedford, Cambridge, Colchester, Newcastle, and Luton NHS Foundation Trusts. Gene-agnostic trio WGS was performed using AI-based variant prioritisation, with subsequent application of a CP gene list. Candidate diagnostic pathogenic (P) or likely pathogenic (LP) variants were reviewed at multidisciplinary meetings and confirmed in an NHS Genomic Laboratory Hub prior to issuing a clinical report. The use of human phenotype ontology (HPO) terms was evaluated to estimate probability of a diagnostic variant using a supervised linear discriminant analysis (PCA + LDA) model.
FINDINGS: 86/157 (54.7%) individuals approached consented to the study. Variants meeting P/LP diagnostic criteria were identified in 11/86 cases (12.8%). 8/86 participants (9.3%) carried variants strongly suggestive of disease causation. Variants of uncertain significance were identified in 27/86 cases (31.4%). In all cases with P/LP variants, findings informed patient prognosis, specialist care, clinical management, and familial recurrence risk. Machine learning approaches were used to segregate the probability of diagnosis for participants based on HPO terms.
INTERPRETATION: WGS is clinically useful for diagnosis and management of genetic conditions associated with CP in the UK. Validation of these findings in a larger cohort is warranted.
FUNDING: Rosetrees Charitable Trust, Isaac Newton Trust, NIHR Cambridge Biomedical Research Centre, and the Wellcome Trust.