RESEARCH ARTICLE Ablepharon Macrostomia Syndrome: A Distinct Genetic Entity Clinically Related to the Group of FRAS–FREM Complex Disorders Denny Schanze, 1 Magdalena Harakalova, 2 Cathy A. Stevens, 3 Francesco Brancati, 4 Bruno Dallapiccola, 5 Peter Farndon, 6 Victor E. F. Ferraz, 7 Donna M. McDonald-McGinn, 8 Elaine H. Zackai, 8 Michael Wright, 9 Stef van Lieshout, 2 Maartje J. Vogel, 2 Mieke M. van Haelst, 2,10 * and Martin Zenker 1,11 ** 1 Institute of Human Genetics, University Hospital Magdeburg, Germany 2 Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands 3 Department of Medical Genetics, T.C. Thompson Children’s Hospital, Chattanooga, Tennessee 4 IRCCS Casa Sollievo della Sofferenza Hospital, Mendel Laboratory, Rome, Italy 5 Bambino Gesu ` Children Hospital, IRCCS, Rome, Italy 6 Clinical Genetics Unit, Birmingham Women’s Healthcare Trust, Birmingham, United Kingdom 7 Departamento de Genetica, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Brazil 8 Clinical Genetics Center, The Children’s Hospital of Philadelphia, 34th St. & Civic Center Blvd, Philadelphia, Pennsylvania 9 Northern Genetics Service, Newcastle upon Tyne Hospitals, UK 10 Section of Genomic Medicine, Imperial College London, London, UK 11 Institute of Human Genetics, University Hospital Erlangen, Germany Manuscript Received: 30 July 2012; Manuscript Accepted: 2 June 2013 Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare congenital malformation syndrome. It overlaps clinically with Fraser syndrome (FS; OMIM 219000), which is known to be caused by mutations in either FRAS1, FREM2, or GRIP1, encoding components of a protein complex that plays a role in epidermal–dermal interactions during morphogenetic processes. We explored the hypothesis that AMS might be either allelic to FS or caused by mutations in other genes encoding known FRAS1 interacting partners. No mutation in either of these genes was found in a cohort of 11 patients with AMS from 10 unrelated families. These findings demonstrate that AMS is genetically distinct from FS. It is proposed that it constitutes a separate entity within the group of FRAS–FREM complex disorders. Ó 2013 Wiley Periodicals, Inc. Mieke M. van Haelst and Martin Zenker contributed equally to this work. Conflict of interest: none. Ã Correspondence to: Dr. Mieke M. van Haelst, Department of Medical Genetics, Lundlaan 6, 3584 EA Utrecht, The Netherlands. E-mail: m.vanhaelst@umcutrecht.nl ÃÃ Correspondence to: Prof. Dr. med. Martin Zenker, Institute of Human Genetics, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. E-mail: martin.zenker@med.ovgu.de Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2013 DOI 10.1002/ajmg.a.36119 How to Cite this Article: Schanze D, Harakalova M, Stevens CA, Brancati F, Dallapiccola B, Farndon P, Ferraz VEF, McDonald-McGinn DM, Zackai EH, Wright M, van Lieshout S, Vogel MJ, van Haelst MM, Zenker M. 2013. Ablepharon macrostomia syndrome: a distinct genetic entity clinically related to the group of FRAS–FREM complex disorders. Am J Med Genet Part A. Ó 2013 Wiley Periodicals, Inc. 1