Journal article
A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature
American journal of medical genetics. Part A, Vol.191(5), pp.1227-1239
05/2023
DOI: 10.1002/ajmg.a.63130
PMCID: PMC10081944
PMID: 36751037
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.
Details
- Title: Subtitle
- A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature
- Creators
- Alanna Strong - Children's Hospital of PhiladelphiaSoumya Rao - University of Missouri–Kansas CitySandra von Hardenberg - Medizinische Hochschule HannoverDong Li - Children's Hospital of PhiladelphiaLiza L Cox - University of Missouri–Kansas CityPaul C Lee - Washington University in St. LouisLi Q Zhang - University of Missouri–Kansas CityWaheed Awotoye - University of IowaTamir Diamond - University of PennsylvaniaJessica Gold - Children's Hospital of PhiladelphiaCatherine Gooch - Washington University in St. LouisLord Jephthah Joojo Gowans - Kwame Nkrumah University of Science and TechnologyHakon Hakonarson - University of PennsylvaniaAnne Hing - University of WashingtonKathleen Loomes - University of PennsylvaniaNicole Martin - Hospital for Sick ChildrenMary L Marazita - University of PittsburghTarja Mononen - Kuopio University HospitalDavid Piccoli - University of PennsylvaniaRolph Pfundt - Radboud University NijmegenSalmo Raskin - Assistance Center for Cleft Lip and Palate (CAIF), Curitiba, Puerto Rico, Brazil.Stephen W Scherer - University of TorontoNara Sobriera - Johns Hopkins University School of MedicineCourtney Vaccaro - Children's Hospital of PhiladelphiaXiang Wang - Children's Hospital of PhiladelphiaDeborah Watson - Children's Hospital of PhiladelphiaRosanna Weksberg - Hospital for Sick ChildrenElizabeth Bhoj - Children's Hospital of PhiladelphiaJeffrey C Murray - University of IowaAndrew C Lidral - Lidral Orthodontics, Rockford, Michigan, USA.Azeez Butali - Roy J. and Lucille A. Carver College of MedicineMichael F Buckley - Prince of Wales HospitalTony Roscioli - UNSW SydneyDavid A Koolen - Radboud University NijmegenLaurie H Seaver - Helen DeVos Children's HospitalCynthia A Prows - Cincinnati Children's Hospital Medical CenterRolf W Stottmann - Cincinnati Children's Hospital Medical CenterTimothy C Cox - University of Missouri–Kansas City
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.191(5), pp.1227-1239
- DOI
- 10.1002/ajmg.a.63130
- PMID
- 36751037
- PMCID
- PMC10081944
- NLM abbreviation
- Am J Med Genet A
- eISSN
- 1552-4833
- Grant note
- X01-HL136465 / NIH HHS #FY 98-0718 / March of Dimes Foundation Cleft Palate Foundation U01HG011172 / eMERGE R01 DE027091 / NIH HHS Stowers Family Foundation Endowment R01-016148 / NIH HHS X01-HL132363 / NIH HHS R37-DE008559 / NIH HHS AU/1/BA51117 / Australian National Health & Medical Research Council University of Iowa K08DK128606 / NIH HHS R01HG010166 / eMERGE R01-DE014667 / NIH HHS Autism Speaks R01 DE027879 / NIH HHS #6-FY01-616 / March of Dimes Foundation Hospital for Sick Children
- Language
- English
- Electronic publication date
- 02/07/2023
- Date published
- 05/2023
- Academic Unit
- Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984366043502771
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