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Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate.

作者信息

Rammos Alexandros, Blakey Rachel, Dennison Charlotte A, Lewis Sarah J, Ali Nabila, Davies Amy, Wren Yvonne, Humphries Kerry, Sandy Jonathan, Rees Elliott, Kendall Kimberley Marie, Sharp Gemma C, Owen Michael J, van den Bree Marianne B M, Stergiakouli Evie

机构信息

Cleft Collective, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.

Population Health Sciences, Bristol Medical School, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.

出版信息

Hum Mol Genet. 2025 Sep 3;34(18):1563-1574. doi: 10.1093/hmg/ddaf115.


DOI:10.1093/hmg/ddaf115
PMID:40662303
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12409624/
Abstract

Cleft lip and/or palate (CL/P) is the most common craniofacial congenital anomaly and has been associated with higher risk of neurodevelopmental and behavioural problems indicating potential shared genetic factors between CL/P and neurodevelopmental disorders. In this study, we aimed to determine the prevalence of neurodevelopmental copy number variants (CNV) in children with CL/P and their link to early developmental and behavioural problems. Using data from the Cleft Collective, the largest UK-based national cohort study of children with CL/P, we determined the rates of neurodevelopmental CNVs in children with CL/P comparing them to the general population, explored differences by cleft type and investigated risk of developmental delays and behavioural problems among those with CL/P and neurodevelopmental CNVs. Children with CL/P had a higher prevalence of neurodevelopmental CNVs than participants in four population-based samples (3.7% vs 2.3% in the Avon Longitudinal Study of Parents and Children (ALSPAC), 2.0% in Born in Bradford (BiB), 2.3% in Millenium Cohort Study (MCS), 1.7% in UK Biobank, ORs(95%CIs): ALSPAC = 1.56(1.18-2.06), BiB = 1.84(1.37-2.45), MCS = 1.59(1.19-2.11), UK Biobank = 2.15(1.68-2.71). Children with cleft palate only were 3 times more likely to have a neurodevelopmental CNV (95%CIs1.50-6.59, p = 0.03) than children with cleft lip only. Furthermore, children with CL/P and neurodevelopmental CNVs were more likely to experience early developmental delays and behavioural problems by age 5 compared to children with CL/P and without neurodevelopmental CNVs. These findings highlight that genetic testing ascertaining the presence of neurodevelopmental CNVs might be helpful in early identification of developmental needs in children with CL/P.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c92/12409624/59c8e4dfae01/ddaf115f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c92/12409624/59c8e4dfae01/ddaf115f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c92/12409624/59c8e4dfae01/ddaf115f1.jpg

相似文献

[1]
Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate.

Hum Mol Genet. 2025-9-3

[2]
Evaluating structure and content of parent-implemented early logopaedic intervention models following the three stages of communicative development in children with cleft lip and/or palate: Systematic literature review with narrative synthesis.

Int J Lang Commun Disord. 2024

[3]
A systematic review of early speech interventions for children with cleft palate.

Int J Lang Commun Disord. 2022-1

[4]
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BMC Oral Health. 2024-2-5

[5]
The impact of early special educational needs provision on later hospital admissions, school absence and education attainment: A target trial emulation study of children with isolated cleft lip and/or palate.

PLoS One. 2025-7-16

[6]
Prevalence of Treatment of Early Childhood Caries among Children with Cleft Lip and/or Cleft Palate in Manitoba.

Cleft Palate Craniofac J. 2024-8

[7]
Diagnostic Utility of Trio-Exome Sequencing for Children With Neurodevelopmental Disorders.

JAMA Netw Open. 2025-3-3

[8]
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Int J Lang Commun Disord. 2024

[9]
Tooth abnormalities associated with non-syndromic cleft lip and palate: systematic review and meta-analysis.

Clin Oral Investig. 2022-8

[10]
Pattern of Cleft Lip and Palate Clefts at a Tertiary Care Hospital in Saudi Arabia.

Cleft Palate Craniofac J. 2024-8-2

本文引用的文献

[1]
Early Manifestations of Neurodevelopmental Copy Number Variants in Children: A Population-Based Investigation.

Biol Psychiatry. 2025-3-14

[2]
Comparison of autism domains across thirty rare variant genotypes.

EBioMedicine. 2025-2

[3]
Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications.

Mol Psychiatry. 2025-2

[4]
The Cleft Collective: protocol for a longitudinal prospective cohort study.

BMJ Open. 2024-7-5

[5]
The heterogeneous genetic architectures of orofacial clefts.

Trends Genet. 2024-5

[6]
Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.

HGG Adv. 2023-10-12

[7]
Orofacial Clefts: Genetics of Cleft Lip and Palate.

Genes (Basel). 2023-8-9

[8]
Participation bias in the UK Biobank distorts genetic associations and downstream analyses.

Nat Hum Behav. 2023-7

[9]
DRAGON-Data: a platform and protocol for integrating genomic and phenotypic data across large psychiatric cohorts.

BJPsych Open. 2023-2-8

[10]
Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Nat Genet. 2023-2

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