学術雑誌論文

学術雑誌論文

text

Human Molecular Genetics. 2024, 33(22), p. 1975-1985

Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial syndrome with a variant in ACTB

Oxford University Press

英語

text

2024-09-13

https://doi.org/10.1093/hmg/ddae133

This is a pre-copyedited, author-produced version of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Tsujimoto T., Ou Y., Suzuki M., et al. Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial syndrome with a variant in ACTB, Human Molecular Genetics 33, 1975 (2024) is available online at: https://doi.org/10.1093/hmg/ddae133.

Craniofacial anomalies encompassing the orofacial cleft are associated with > 30% of systemic congenital malformations. Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in patients with BWCFF. In this study, we identified a missense variant (c.1043C > T: p.S348L) in the ACTB gene of a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line and Xenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize to the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we discovered that the mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF.

103591

Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial syndrome with a variant in ACTB

Oxford University Press

英語

2024-09-13

Human Molecular Genetics

33

22

1975

1985

https://doi.org/10.1093/hmg/ddae133

https://hdl.handle.net/11094/103591