Orthod Craniofac Res. 2019;22(Suppl. 1):163–167. wileyonlinelibrary.com/journal/ocr | 163 © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 | INTRODUCTION Craniofacial development is a highly coordinated process under a tight genetic and epigenetic control. Any mishaps during the early developmental process will result in a range of craniofacial malfor- mations. 1 Craniofacial microsomia (CFM) is a congenital disorder with unilateral or bilateral defects in the derivatives of the first and sec- ond branchial arches. The phenotypic presentation of these patients includes defects of the external ear, middle ear, temporomandibular joint, mandible, muscles of facial expression and mastication leading to Received: 29 November 2018 | Revised: 19 December 2018 | Accepted: 4 December 2018 DOI: 10.1111/ocr.12259 SUPPLEMENT ARTICLE A novel nonsense substitution identified in the AMIGO2 gene in an Occulo-Auriculo-Vertebral spectrum patient Shankar Rengasamy Venugopalan 1 | Emily Farrow 2 | Pedro A. Sanchez–Lara 3,4 | Stephen Yen 4 | Michael Lypka 2 | Shao Jiang 2 | Veerasathpurush Allareddy 5 Shankar Rengasamy Venugopalan and Emily Farrow these authors contributed equally. 1 School of Dentistry, University of Missouri Kansas City, Kansas City, Missouri 2 Children’s Mercy Hospitals, Kansas City, Missouri 3 Cedars–Sinai Medical Center, Los Angeles, California 4 Children’s Hospital Los Angeles, Los Angeles, California 5 College of Dentistry, University of Illinois at Chicago, Chicago, Illinois Correspondence Shankar Rengasamy Venugopalan, Department of Orthodontics and Dentofacial Orthopedics, School of Dentistry University of Missouri Kansas City, Kansas City, MO. Email: rengavs@umkc.edu Funding information American Association of Orthodontist Foundation; University of Missouri Kansas City Center for Excellence in the Study of Dental and Musculoskeletal Tissues Structured Abstract Objective: Craniofacial microsmia is the second most common congenital disorder with mostly unilateral defects of ear, temporomandibular joint, mandible, and mus- cles of facial expression and mastication. The objective of this study was to identify, if there were any, de novo germline or somatic variants in a patient with Occulo- Auriculo-Vertebral Spectrum (OAVS) using whole-exome sequencing. Settings and Sample Population: Trio/Family-based study of an OAVS proband. Materials and Methods: Children’s Mercy Hospital Institutional Review Board ap- proved this study and a request-to-rely was procured from the University of Missouri Kansas City IRB. Informed assent/consent was obtained for all family members prior to any research activities. The peripheral blood/affected side tissues from corrective surgery of the proband and peripheral blood samples from unaffected parents were collected. The isolated genomic DNA were enriched for exomes and sequenced on an Illlumina HiSeq 2500 instrument yielding paired-end 125 nucleotide reads (84X coverage). Gapped alignment to reference sequences (GRCh37.p5) was performed with BWA and the GATK and analysis completed using custom-developed software. Results: Analyses revealed that the proband carried a de novo germ line nonsense substitution (c.901C>T) in AMIGO2 gene, and missense substitutions in ZCCHC14 (c.1198C>T), and in SZT2 genes (c.2951C>T). Conclusions: The nonsense substitution in AMIGO2 gene introduces a premature stop codon possibly rendering the gene non-functional via nonsense-mediated path- way decay—therefore considered a stronger candidate. Further functional studies are required to confirm whether loss-of-function variants in AMIGO2 can cause OAVS. KEYWORDS AMIGO2, craniofacial microsomia, Goldenhar Syndrome, Occulo-Auriculo-Vertebral Spectrum