Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines

JAMA Pediatrics, Journal Year: 2023, Volume and Issue: 177(5), P. 472 - 472

Published: March 6, 2023

Importance Exome sequencing is a first-tier diagnostic test for individuals with neurodevelopmental disorders, including intellectual disability/developmental delay and autism spectrum disorder; however, this recommendation does not include cerebral palsy. Objective To evaluate if the yield of exome or genome in palsy similar to that other disorders. Data Sources The study team searched PubMed studies published between 2013 2022 using genetic testing terms. were analyzed during March 2022. Study Selection Studies performing at least 10 participants included. fewer than reporting variants detected by tests excluded. Consensus review was performed. initial search identified 148 studies, which 13 met inclusion criteria. Extraction Synthesis extracted 2 investigators pooled random-effects meta-analysis. Incidence rates corresponding 95% CIs prediction intervals calculated. Publication bias evaluated Egger test. Variability included assessed via heterogeneity I statistic. Main Outcomes Measures primary outcome (rate pathogenic/likely pathogenic variants) across studies. Subgroup analyses performed based on population age use exclusion criteria patient selection. Results Thirteen consisting 2612 overall 31.1% (95% CI, 24.2%-38.6%; = 91%). higher pediatric populations (34.8%; 28.3%-41.5%) adult (26.9%; 1.2%-68.8%) among used selection (42.1%; 36.0%-48.2%) those did (20.7%; 12.3%-30.5%). Conclusions Relevance In systematic meta-analysis, disorders recommended as standard care. from meta-analysis provide evidence support current evaluation

Language: Английский

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Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(9), P. 542 - 555

Published: Aug. 3, 2023

Language: Английский

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Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 585 - 594

Published: March 29, 2024

Language: Английский

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Relationship Between Nutritional Status and Severity of Cerebral Palsy: A Multicentre Cross-Sectional Study

Journal of Rehabilitation Medicine, Journal Year: 2023, Volume and Issue: 55, P. jrm00367 - jrm00367

Published: Jan. 12, 2023

Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and severity of CP is unclear.To describe characteristics CP, to explore children.This multicentre cross-sectional study included China. Weight height were measured converted z-scores. Gross Motor Function Classification System (GMFCS), Eating Drinking Ability (EDACS), Subjective Global Assessment (SGNA), social life ability, blood indicators tested.All 1,151 participants given oral-feeding 50.8% them demonstrated undernutrition. Compared those GMFCS or EDACS levels I-III, odds moderate severe undernutrition 2.6 8.9 times higher IV V, 4.3 12.6 respectively. Except for serum 25-hydroxyvitamin D, no significant differences found among normal, undernourished overnourished groups.Degrees correlated eating drinking dysfunction gross motor impairment. Blood may not reflect CP.

Language: Английский

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A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 22, 2025

Most current information about neurological disorders and diseases is derived from direct patient animal studies. However, studies in many cases do not allow replication of the early stages disease and, therefore, offer limited opportunities to understand progression. On other hand, although use models allows us study mechanisms disease, they present significant limitations developing drugs for humans. Recently, 3D-cultured vitro human pluripotent stem cells have surfaced as a promising system. They potential connect findings with those models. In this comprehensive review, we discuss their application modeling neurodevelopmental conditions such Down Syndrome or Autism, neurodegenerative Alzheimer's Parkinson's, viral like Zika virus HIV. Furthermore, will different used prenatal exposure abuse, well challenges that must be met transform landscape research on brain disorders.

Language: Английский

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BCL11B-related disease: a single phenotypic entity?

European Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Neurological Diseases Caused by Loss of Transfer RNA Modifications: Commonalities in Their Molecular Pathogenesis

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169047 - 169047

Published: March 1, 2025

Language: Английский

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Cerebral palsy and related neuromotor disorders: Overview of genetic and genomic studies

Molecular Genetics and Metabolism, Journal Year: 2021, Volume and Issue: 137(4), P. 399 - 419

Published: Nov. 8, 2021

Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture, beginning early in development. Early family and twin studies more recent genomic investigations clearly demonstrate that genetic factors of major effect contribute to the etiology CP. Most copy number variants small alterations nucleotide sequence cause CP arise as result de novo mutations, so estimate heritability on basis recurrence frequency within families substantially underestimate contributions etiology. At least 4% patients with typical have disease-causing CNVs, at 14% single indels. The rate pathogenic lesions probably than twice high among who atypical CP, i.e., neuromotor dysfunction additional neurodevelopmental abnormalities malformations, MRI findings medical history are not characteristic perinatal insult. Mutations many different loci can produce CP-like phenotype. importance minor epigenetic modifications producing multifactorial predisposition less clear. Recognizing specific an affected individual essential providing optimal clinical management. An etiological diagnosis provides "enhanced compass" improves overall well-being, facilitates access educational social services, permits accurate counseling, and, for subset such those underlying inherited metabolic disorders, may make precision therapy targets pathophysiology available. Trio exome sequencing assessment trio genome bioinformatics analysis variants, indels, clinically indicated initial workup patients, especially malformations abnormalities.

Language: Английский

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Wybutosine hypomodification of tRNAphe activates HERVK and impairs neuronal differentiation

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109748 - 109748

Published: April 16, 2024

We previously reported that loss of function TYW1 led to cerebral palsy with severe intellectual disability through reduced neural proliferation. However, whether affects differentiation is unknown. In this study, we first demonstrated blocked the formation OHyW in tRNA

Language: Английский

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Genetic Testing for Global Developmental Delay in Early Childhood

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(6), P. e2415084 - e2415084

Published: June 5, 2024

Importance Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment the core symptom, despite pivotal role of genetic factors in GDD development, understanding them remains limited. Objectives To assess utility detection patients with to examine potential molecular pathogenesis identify targets intervention. Design, Setting, Participants This multicenter, prospective cohort study enrolled aged 12 60 months from 6 centers China July 4, 2020, August 31, 2023. underwent trio whole exome sequencing (trio-WES) coupled copy number variation (CNV-seq). Bioinformatics analysis was used unravel therapeutic targets. Main Outcomes Measures The main outcomes this involved enhancing rate positive diagnosis GDD, broadening scope testing indications, investigating underlying pathogenesis. classification children into levels cognitive based on quotient assessed using Gesell scale. Results encompassed 434 (262 [60%] male; mean [SD] age, 25.75 [13.24] months) degrees impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), profound (73 [17%]). combined use trio-WES CNV-seq resulted 61% rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), or (OR, 1.69; 1.05-2.70), age between 24 1.57; 1.05-2.35) were associated higher risk carrying variants. Additionally, bioinformatics suggested that variants may induce alterations brain development function, which give rise impairment. Moreover, an association found dopaminergic pathway Conclusions Relevance In combining demonstrable, instrumental strategy advancing GDD. close among variations, phenotypes contributed valuable insights Notably, emerged as promising focal point future precision medical interventions

Language: Английский

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