The pleiotropic spectrum of proximal 16p11.2 CNVs.
Details
Serval ID
serval:BIB_BD9ABD973D1F
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
The pleiotropic spectrum of proximal 16p11.2 CNVs.
Journal
American journal of human genetics
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Publication state
Published
Issued date
07/11/2024
Peer-reviewed
Oui
Volume
111
Number
11
Pages
2309-2346
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Publication Status: ppublish
Abstract
Recurrent genomic rearrangements at 16p11.2 BP4-5 represent one of the most common causes of genomic disorders. Originally associated with increased risk for autism spectrum disorder, schizophrenia, and intellectual disability, as well as adiposity and head circumference, these CNVs have since been associated with a plethora of phenotypic alterations, albeit with high variability in expressivity and incomplete penetrance. Here, we comprehensively review the pleiotropy associated with 16p11.2 BP4-5 rearrangements to shine light on its full phenotypic spectrum. Illustrating this phenotypic heterogeneity, we expose many parallels between findings gathered from clinical versus population-based cohorts, which often point to the same physiological systems, and emphasize the role of the CNV beyond neuropsychiatric and anthropometric traits. Revealing the complex and variable clinical manifestations of this CNV is crucial for accurate diagnosis and personalized treatment strategies for carrier individuals. Furthermore, we discuss areas of research that will be key to identifying factors contributing to phenotypic heterogeneity and gaining mechanistic insights into the molecular pathways underlying observed associations, while demonstrating how diversity in affected individuals, cohorts, experimental models, and analytical approaches can catalyze discoveries.
Keywords
Humans, Chromosomes, Human, Pair 16/genetics, DNA Copy Number Variations, Intellectual Disability/genetics, Phenotype, Genetic Pleiotropy, Autism Spectrum Disorder/genetics, Schizophrenia/genetics, Chromosome Disorders/genetics, Chromosome Deletion, multi-system disorder, penetrance, pleiotropy, proximal 16p11.2 BP4-5 CNV, structural variant, variable expressivity
Pubmed
Open Access
Yes
Create date
04/10/2024 14:22
Last modification date
15/11/2024 20:36