Abstract

Background

This study aimed to characterize the frequency of RAI1 genetic aberrations associated with Smith–Magenis syndrome (SMS), in a large cohort of autism spectrum disorder (ASD) whole-genome sequencing samples. We aimed to determine the frequencies of RAI1 single-nucleotide variants (SNVs) and copy number variants (CNVs).

Results

We report a 2.5 × enrichment of the major deletion and a > 5 × enrichment of the frameshift variants as compared to the known prevalence of SMS 1/15,000. Additionally, we report a significant enrichment of RAI1 rare missense variants in ASD subjects with respect to controls (54 variants/6080 ASD subjects and 6 variants/2541 controls, p-value < 0.002, OR 3.78, CI 1.62–8–81).

Conclusions

The SMS phenotype including circadian dysregulation and associated sleep disturbances is mainly caused by RAI1 haploinsufficiency. Sleep disturbances as seen in SMS may overlap in ASD, especially in patients with consequential variants in RAI1 gene.

Details

Title
Retinoic Acid-Induced 1 gene variants associated with Smith–Magenis syndrome circadian phenotypes enriched in autism spectrum disorder: whole-genome sequencing study
Author
Smieszek, Sandra Paulina 1   VIAFID ORCID Logo 

1  Vanda Pharmaceuticals Inc, Washington, USA (GRID:grid.476806.b) (ISNI:0000 0004 4670 3182) 
Pages
55
Publication year
2024
Publication date
Dec 2024
Publisher
Springer Nature B.V.
ISSN
11108630
e-ISSN
20902441
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s43042-024-00508-3
ProQuest document ID
3050367949
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.