AMOTL1 encodes angiomotin-like protein 1, an actin-binding protein that regulates cell polarity, adhesion, and migration. The role of AMOTL1 in human disease is equivocal. We report a large cohort of individuals harboring heterozygous AMOTL1 variants and define a core phenotype of orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations in individuals with variants in AMOTL1 affecting amino acids 157-161, a functionally undefined but highly conserved region. Three individuals with AMOTL1 variants outside this region are also described who had variable presentations with orofacial clefting and multi-organ disease. Our case cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157-161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
Kids First Partner Institutions
The Kids First Data Resource Center (“DRC”) comprises partnered institutions supported by the NIH Common Fund under Award Number U2CHL138346 as part of the Common Fund’s Gabriella Miller Kids First Pediatric Research Program (“Kids First”). All content, terms and conditions and policies associated with the DRC Portal and Website (the “Services”) are produced by the DRC. The views and opinions of authors expressed on the Services do not necessarily state or reflect those of the National Institutes of Health (“NIH”) or the U.S. government. Furthermore, the NIH does not endorse or promote any DRC entity or any of its products or services nor guarantees the products, services, or information provided by the DRC.
© 2024 Gabriella Miller Kids First Data Resource Center. All rights reserved.