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Updated: Oct 25, 2025
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Analysis of Craniomaxillofacial Malformations in Mice Using Three-dimensional Microcomputed Tomography
Published on: January 17, 2025
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Haploinsufficiency of SF3B2 causes craniofacial microsomia
Andrew T Timberlake1, Casey Griffin2, Carrie L Heike3,4
1Hansjorg Wyss Department of Plastic and Reconstructive Surgery, NYU Langone Medical Center, New York, NY, USA. andrew.timberlake@nyumc.org.
Nature Communications
|August 4, 2021
Summary
Genetic variants in SF3B2 are a leading cause of craniofacial microsomia (CFM). This study identifies SF3B2 mutations in individuals with CFM, revealing a key factor in this common congenital facial anomaly.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- Craniofacial microsomia (CFM) is a common congenital facial anomaly with an unknown genetic cause.
- Understanding the genetic basis of CFM is crucial for diagnosis and potential therapeutic strategies.
Purpose of the Study:
- To identify the genetic etiology of craniofacial microsomia (CFM).
- To investigate the role of SF3B2 variants in the development of CFM.
Main Methods:
- Whole-exome or whole-genome sequencing in 146 kindreds with sporadic or familial CFM.
- Analysis of loss-of-function variants in SF3B2.
- Functional studies using Xenopus morpholino knockdown of SF3B2.
Main Results:
- A significant burden of loss-of-function variants in SF3B2 was identified in CFM probands.
- Twenty individuals from seven kindreds harbored de novo or transmitted haploinsufficient SF3B2 variants.
- SF3B2 knockdown in Xenopus disrupted cranial neural crest development and caused craniofacial cartilage defects.
Conclusions:
- Haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining a significant percentage of sporadic and familial cases.
- Mutations in SF3B2 and spliceosome dysfunction are linked to impaired neural crest development in congenital craniofacial disease.
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