title: MSX1 mutations and associated disease phenotypes: genotype-phenotype relations.
abstract: The Msx1 transcription factor is involved in multiple epithelial-mesenchymal interactions during vertebrate embryogenesis. It has pleiotropic effects in several tissues. In humans, MSX1 variants have been related to tooth agenesis, orofacial clefting, and nail dysplasia. We correlate all MSX1 disease causing variants to phenotypic features to shed light on this hitherto unclear association. MSX1 truncations cause more severe phenotypes than in-frame variants. Mutations in the homeodomain always cause tooth agenesis with or without other phenotypes while mutations outside the homeodomain are mostly associated with non-syndromic orofacial clefts. Downstream effects can be further explored by the edgetic perturbation model. This information provides new insights for genetic diagnosis and for further functional analysis of MSX1 variants.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Von den Hoff
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lange
authors.affiliation: Department of Orthodontics, University of Groningen and University Medical Center of Groningen, Groningen, The Netherlands.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Oral Health Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Carine E L
authors.initials: CE
authors.lastname: Carels
mesh_terms: D000818:Animals; D000848:Anodontia / Q000175:diagnosis / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D009056:Mouth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009264:Nails, Malformed / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human