Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
8-5-2025
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2427085122
PMID
40720646
PMCID
PMC12337293
PubMedCentral® Posted Date
7-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that neurodevelopmental dysfunction can be driven by variation in circadian clock genes in a subset of individuals.
Keywords
ARNTL Transcription Factors, Humans, Animals, Circadian Rhythm, Neurodevelopmental Disorders, Male, Period Circadian Proteins, Female, Autism Spectrum Disorder, Child, Developmental Disabilities, Drosophila melanogaster, BMAL1, neurodevelopmental disorder, circadian rhythms, developmental delay, Drosophila
Published Open-Access
yes
Recommended Citation
Cuddapah, Vishnu Anand; Chen, Dechun; Cho, Bumsik; et al., "Rare Variants in BMAL1 Are Associated With a Neurodevelopmental Syndrome" (2025). Duncan NRI Faculty and Staff Publications. 147.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/147
Included in
Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons