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

Infantile-onset choreo-dystonia due to a novel homozygous truncating HPCA variant: A first report from India DOI
Vikram V. Holla, Sandeep Gurram, Sneha Kamath

et al.

Parkinsonism & Related Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 107329 - 107329

Published: Feb. 1, 2025

Language: Английский

Citations

0
Neurological Diseases Caused by Loss of Transfer RNA Modifications: Commonalities in Their Molecular Pathogenesis DOI
Takeshi Chujo, Kazuhito Tomizawa

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

Published: March 1, 2025

Language: Английский

Citations

0
Genetic Alterations in Atypical Cerebral Palsy Identified Through Chromosomal Microarray and Exome Sequencing DOI Open Access
Ji Yoon Han, Jin Gwack, Jong Hun Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2929 - 2929

Published: March 24, 2025

This study investigated the genetic causes of atypical cerebral palsy (CP) through chromosomal microarray (CMA) and exome sequencing (ES) in a cohort 10 Korean patients to identify variants expand spectrum mutations associated with palsy. Whole ES and/or genome (GS) after routine karyotyping CMA was performed causative CP. In cases CP, scoliosis kyphosis, ranging from mild severe, were present all patients. Epilepsy comorbidity seven (70%), intellectual disability (ID) observed varying degrees. identified three copy number variations (CNVs), including 15q11.2 microdeletion (n = 1), 17p11.2 duplication 12p13.33p11.23 duplication/18p11.32 six likely pathogenic (LPVs) or (PVs) detected SLC2A1, PLAA, CDC42BPB, CACNA1D, ALG12, SACS genes 6). These findings emphasize significance incorporating testing into diagnostic process for CP improve our understanding its molecular basis inform personalized treatment strategies. To further advance this research, future studies should focus on exploring genotype-phenotype correlations, assessing functional impact variants, increasing sample size validate patterns.

Language: Английский

Citations

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The Genetics of Cerebral Palsy DOI
Marije Meuwissen, Katrien Janssens

Published: Jan. 1, 2025

Language: Английский

Citations

0
Genetic testing in cerebral palsy with clinical and neuroimaging variables DOI Creative Commons
Esther Tantsis, Shekeeb S. Mohammad, Simon Paget

et al.

Developmental Medicine & Child Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Abstract Aim To optimize genetic testing in children with cerebral palsy (CP) by using clinical and magnetic resonance imaging (MRI) variables. Method In this mixed methods study, we surveyed current approaches to Australian clinicians involved the diagnosis of CP. Using an international expert panel explored 78 variables, determine which variables were thought be supportive monogenic We tested a retrospective cohort 100 CP, whom 21 had cause Results Forty‐five replied survey practice, 91% agreed that has role although 47% there was inadequate guidance on patients test. The reached 75% agreement for 30 out 14 against Retrospective CP revealed dysmorphic features (odds ratio [OR] = 7.50; 95% confidence interval [CI] 1.88–29.85) intellectual disability (OR 4.86; CI 1.29–18.30) more common those MRI being compatible picture feature least 0.14; 0.05–0.41). Interpretation Genetic determining aetiology; however, is no consensus who should tested. used methodology found features, disability, ‘MRI not picture’ are most

Language: Английский

Citations

0
Integrated metabolomics and proteomics analysis in children with cerebral palsy exposed to botulinum toxin-A DOI
Zhaofang Chen, Tingting Peng,

Mengru Zhong

et al.

Pediatric Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

Citations

0
BCL11B‐Related Dystonia: Further Evidence of an Emerging Cause of Childhood‐Onset Generalized Dystonia DOI
Giacomo Garone, Alessandro Capuano, Donato Amodio

et al.

Movement Disorders Clinical Practice, Journal Year: 2024, Volume and Issue: 11(7), P. 897 - 901

Published: May 27, 2024

Since original data of this study consist medical records, they are not publicly available due to privacy restrictions. The that support the findings on request from corresponding author. TABLE S1. Whole exome sequencing statistics and output. S2. Immunological profile proband. Please note: publisher is responsible for content or functionality any supporting information supplied by authors. Any queries (other than missing content) should be directed author article.

Language: Английский

Citations

3
Genetic Testing for Global Developmental Delay in Early Childhood DOI Creative Commons
Jiamei Zhang, Yiran Xu, Yun Liu

et al.

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

Citations

3
Cerebral Palsy: An Overview of Etiology, Types and Comorbidities DOI Open Access
Joshua Vova

OBM Neurobiology, Journal Year: 2022, Volume and Issue: 6(2), P. 1 - 1

Published: Feb. 21, 2022

Cerebral Palsy (CP) is the most frequent cause of childhood disability. CP occurs in 1 out every 345 children United States. primarily a motor disease that result an insult to brain during prenatal or early postnatal period when still developing. not single but physical description impairments originate from multiple etiologies. This article briefly discusses etiologies, classification and management neurologic medical comorbidities are associated with CP. Proactive can assist minimizing morbidity maximizing outcomes improving quality life.

Language: Английский

Citations

14
Clinical Characteristics Suggestive of a Genetic Cause in Cerebral Palsy: A Systematic Review DOI Creative Commons
Anna M. Janzing, Erik A. Eklund, Tom J. de Koning

et al.

Pediatric Neurology, Journal Year: 2024, Volume and Issue: 153, P. 144 - 151

Published: Feb. 2, 2024

Cerebral palsy (CP) is a clinical diagnosis and was long categorized as an acquired disorder, but more genetic etiologies are being identified. This review aims to identify the characteristics that associated with CP aid clinicians in selecting candidates for testing.

Language: Английский

Citations

2