FOXI3 pathogenic variants cause one form of craniofacial microsomia.

Autor: Mao K; School of Engineering Medicine, Beihang University, Beijing, 100191, China., Borel C; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland., Ansar M; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland.; Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, 1004, Lausanne, Switzerland., Jolly A; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Makrythanasis P; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland.; Laboratory of Medical Genetics, Medical School, University of Athens, Athens, Greece.; Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Froehlich C; CeGaT GmbH and Praxis für Humangenetik Tuebingen, Tuebingen, 72076, Germany., Iwaszkiewicz J; Molecular Modeling Group, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland., Wang B; Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, 100144, China., Xu X; School of Engineering Medicine, Beihang University, Beijing, 100191, China.; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China., Li Q; Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China., Blanc X; Medigenome, Swiss Institute of Genomic Medicine, 1207, Geneva, Switzerland., Zhu H; School of Engineering Medicine, Beihang University, Beijing, 100191, China., Chen Q; Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, 100144, China., Jin F; School of Engineering Medicine, Beihang University, Beijing, 100191, China.; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China., Ankamreddy H; Department of Biotechnology, School of Bioengineering, SRMIST, Kattankulathur, Tamilnadu, 603203, India., Singh S; Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA., Zhang H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA., Wang X; School of Engineering Medicine, Beihang University, Beijing, 100191, China.; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China., Chen P; Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China., Ranza E; Medigenome, Swiss Institute of Genomic Medicine, 1207, Geneva, Switzerland., Paracha SA; Anatomy Department, Khyber Medical University Institute of Medical Sciences (KIMS), Kohat, Pakistan., Shah SF; Department of Medicine, KMU Institute of Medical Sciences (KIMS), DHQ Hospital KDA, Kohat, Pakistan., Guida V; Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Piceci-Sparascio F; Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Melis D; Department of Medicine, Surgery, and Dentistry, Università University degli of Studi di Salerno, Salerno, Italy., Dallapiccola B; Medical Genetics and Rare Disease Research Division, Pediatric Cardiology, Medical Genetics Laboratory, Neuropsychiatry, Scientific Rectorate, Bambino Gesù Children Hospital, IRCCS, Rome, Italy., Digilio MC; Sezione di Genetica Medica, Ospedale 'Bambino Gesù', Rome, Italy., Novelli A; Sezione di Genetica Medica, Ospedale 'Bambino Gesù', Rome, Italy., Magliozzi M; Sezione di Genetica Medica, Ospedale 'Bambino Gesù', Rome, Italy., Fadda MT; Department of Maxillo-Facial Surgery, Policlinico Umberto I, Rome, Italy., Streff H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Machol K; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Lewis RA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Zoete V; Molecular Modeling Group, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.; Department of Fundamental Oncology, Ludwig Institute for Cancer Research, Lausanne University, Epalinges, 1066, Switzerland., Squeo GM; Laboratory of Regulatory & Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Prontera P; Medical Genetics Unit, Hospital Santa Maria della Misericordia, Perugia, Italy., Mancano G; Medical Genetics Unit, University of Perugia Hospital SM della Misericordia, Perugia, Italy., Gori G; Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy., Mariani M; Pediatric Department, ASST Lariana, Santa Anna General Hospital, Como, Italy., Selicorni A; Pediatric Department, ASST Lariana, Santa Anna General Hospital, Como, Italy., Psoni S; Laboratory of Medical Genetics, Medical School, University of Athens, Athens, Greece., Fryssira H; Laboratory of Medical Genetics, Medical School, University of Athens, Athens, Greece., Douzgou S; Division of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester, UK.; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Marlin S; Centre de Référence Surdités Génétiques, Hôpital Necker, Institut Imagine, Paris, France., Biskup S; CeGaT GmbH and Praxis für Humangenetik Tuebingen, Tuebingen, 72076, Germany., De Luca A; Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Merla G; Laboratory of Regulatory & Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy., Zhao S; Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China., Cox TC; Departments of Oral & Craniofacial Sciences and Pediatrics, University of Missouri-Kansas City, Kansas City, MO, 64108, USA., Groves AK; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA., Lupski JR; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA., Zhang Q; Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, 100144, China. plastic135@126.com., Zhang YB; School of Engineering Medicine, Beihang University, Beijing, 100191, China. zhangyongbiao@buaa.edu.cn.; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China. zhangyongbiao@buaa.edu.cn., Antonarakis SE; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland. stylianos.antonarakis@unige.ch.; Medigenome, Swiss Institute of Genomic Medicine, 1207, Geneva, Switzerland. stylianos.antonarakis@unige.ch.; iGE3 Institute of Genetics and Genomes in Geneva, Geneva, Switzerland. stylianos.antonarakis@unige.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 11; Vol. 14 (1), pp. 2026. Date of Electronic Publication: 2023 Apr 11.
DOI: 10.1038/s41467-023-37703-6
Abstrakt: Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance.
(© 2023. The Author(s).)
Databáze: MEDLINE
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