A Survey of Compound Heterozygous Variants in Pediatric Cancers and Structural Birth Defects DOI Creative Commons
Dustin B. Miller, Stephen Piccolo

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: March 22, 2021

Compound heterozygous (CH) variants occur when two recessive alleles are inherited and the located at different loci within same gene in a given individual. CH important contributors to many types of recessively diseases. However, studies overlook because identification this type variant requires knowing parent origin for each nucleotide. Using computational methods, haplotypes can be inferred using process called “phasing,” which estimates chromosomal most nucleotides. In paper, we used germline, phased, whole-genome sequencing (WGS) data identify across seven pediatric diseases (adolescent idiopathic scoliosis: n = 16, congenital heart defects: 709, disorders sex development: 79, ewing sarcoma: 287, neuroblastoma: 259, orofacial cleft: 107, syndromic cranial dysinnervation: 172), available as parent-child trios Gabriella Miller Kids First Data Resource Center. Relatively little is understood about genetic underpinnings these We classified “potentially damaging” based on minor allele frequencies (MAF), Combined Annotation Dependent Depletion scores, impact transcription or translation, gene-level disease group compared healthy population. For comparison, also identified homozygous alternate (HA) variants, affect both copies single locus; HA represent an alternative mechanism development do not require phasing. Across all diseases, 2.6% samples had potentially damaging 16.2% variant. Of with average number genes per sample was 1 1.25 samples, 5.1 variant, while 35.6 variant; average, only 4.3% affected common genes. Therefore, seeking putatively disease, should considered potential development. If excluded from analysis, candidate may overlooked.

Language: Английский

Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines DOI
Pedro J. Gonzalez-Mantilla, Yirui Hu, Scott M. Myers

et al.

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

Citations

48
Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy DOI
Darcy Fehlings,

Mehdi Zarrei,

Worrawat Engchuan

et al.

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

Published: March 29, 2024

Language: Английский

Citations

17
Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology DOI
Clare L. van Eyk, Michael Fahey, Jozef Gécz

et al.

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

Published: Aug. 3, 2023

Language: Английский

Citations

28
A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders DOI Creative Commons

Ana Rubio,

L. L. Hamilton,

Marcel Bausch

et al.

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

Citations

1
BCL11B-related disease: a single phenotypic entity? DOI Creative Commons
Juliana Heather Vedovato dos Santos, Rebecca S. Tooze,

Sivagamy Sithambaram

et al.

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

Published: March 3, 2025

Language: Английский

Citations

1
Relationship Between Nutritional Status and Severity of Cerebral Palsy: A Multicentre Cross-Sectional Study DOI Creative Commons
Yiting Zhao, Hongmei Tang, Tingting Peng

et al.

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

Citations

18
Cerebral palsy and related neuromotor disorders: Overview of genetic and genomic studies DOI Creative Commons
Jan M. Friedman, Peter van Essen, Clara van Karnebeek

et al.

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

Citations

29
Wybutosine hypomodification of tRNAphe activates HERVK and impairs neuronal differentiation DOI Creative Commons

Chuanbo Sun,

Ruirui Guo,

Xiangyan Ye

et al.

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

Citations

4
Upregulating mTOR/S6 K Pathway by CASTOR1 Promotes Astrocyte Proliferation and Myelination in Gpam−/−-induced mouse model of cerebral palsy DOI
Zhaofang Chen,

Liru Liu,

Xiaolin Guo

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

Citations

0
Lung-specific SFTPC mutations lead to neurodevelopmental disorders with neuroinflammation DOI
Hanmin Dong,

Congwen Zang,

Lili Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 753, P. 151479 - 151479

Published: Feb. 11, 2025

Language: Английский

Citations

0