@article{b68a658f8972460c9f91c3d35214ee1b,
title = "A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature",
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.",
keywords = "YAP, cleft lip, cleft palate, congenital heart disease, exome sequencing, genome sequencing",
author = "Alanna Strong and Soumya Rao and {von Hardenberg}, Sandra and Dong Li and Cox, {Liza L.} and Lee, {Paul C.} and Zhang, {Li Q.} and Waheed Awotoye and Tamir Diamond and Jessica Gold and Catherine Gooch and Gowans, {Lord Jephthah Joojo} and Hakon Hakonarson and Anne Hing and Kathleen Loomes and Nicole Martin and Marazita, {Mary L.} and Tarja Mononen and David Piccoli and Rolph Pfundt and Salmo Raskin and Scherer, {Stephen W.} and Nara Sobriera and Courtney Vaccaro and Xiang Wang and Deborah Watson and Rosanna Weksberg and Elizabeth Bhoj and Murray, {Jeffrey C.} and Lidral, {Andrew C.} and Azeez Butali and Buckley, {Michael F.} and Tony Roscioli and Koolen, {David A.} and Seaver, {Laurie H.} and Prows, {Cynthia A.} and Stottmann, {Rolf W.} and Cox, {Timothy C.}",
note = "Funding Information: The authors wish to acknowledge the participating families for their time and contribution to this study and to the generosity of all donors who supported this program. The authors also wish to acknowledge the resources of MSSNG (www.mss.ng), Autism Speaks, The Cleft Palate Foundation (AL), and The Centre for Applied Genomics at The Hospital for Sick Children, Toronto, Canada. Special thanks to Drs Lina Moreno Uribe and Aline Petrin, University of Iowa, for sample management and shipment. Funding Information: The authors also wish to acknowledge their funding sources: NIH—K08DK128606 (Alanna Strong), R01 DE027091 (Rolf W. Stottmann), R01 DE027879 (Timothy C. Cox), R01‐DE014667 (Andrew C. Lidral), R37‐DE008559 (Jeffrey C. Murray), R01‐016148, X01‐HL132363, X01‐HL136465 (Mary L. Marazita), eMERGE, U01HG011172, and R01HG010166 (Cynthia A. Prows), the Australian National Health & Medical Research Council—AU/1/BA51117 (Tony Roscioli, Michael F. Buckley, Timothy C. Cox, Jeffrey C. Murray, and Andrew C. Lidral), the March of Dimes Basil O'Connor award #FY 98‐0718 and research grant #6‐FY01‐616 (Andrew C. Lidral), and the Stowers Family Foundation Endowment (Timothy C. Cox). Publisher Copyright: {\textcopyright} 2023 Wiley Periodicals LLC.",
year = "2023",
month = may,
doi = "10.1002/ajmg.a.63130",
language = "English",
volume = "191",
pages = "1227--1239",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
number = "5",
}