Abstract
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.
Original language | English |
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Pages (from-to) | 1227-1239 |
Number of pages | 13 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 191 |
Issue number | 5 |
DOIs | |
State | Published - May 2023 |
Keywords
- YAP
- cleft lip
- cleft palate
- congenital heart disease
- exome sequencing
- genome sequencing