Original Research ARTICLE
Homozygous recessive Versican missense variation is associated with early teeth loss in a Pakistani family
- 1Unità Operativa di Genetica Medica, Dipartimento di Scienze Mediche, Università di Ferrara, Italy
- 2Centro di Ricerca per lo Studio delle Malattie Parodontali e Peri-implantari, Università degli Studi di Ferrara, Italy
- 3Istituto di genetica molecolare (IGM), Italy
- 4Beijing Genomics Institute (BGI), China
- 5Klinik für Parodontologie, Zahnklinik, Medizinische Fakultät, Universität Bern, Switzerland
- 6Azienda Ospedaliero Universitaria di Ferrara, Italy
- 7Department of Clinical Medicine, Public Health, Life Sciences and the Environment, University of L'Aquila, Italy
- 8National Institute for Health, Migration and Poverty (NIHMP), Italy
- 9Dubowitz Neuromuscular Centre, Great Ormond Street Institute of Child Health (ICH), University College London, United Kingdom
Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin, in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous mutation in the VCAN gene. Dominant splicing mutations in VCAN are known as causing Wagner syndrome or vitreoretinopathy. In these two patients we explored teeth morphology, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the older brother while parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense mutation genotype impairs the normal morphology of the tooth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding the phenotype mutation scenario of VCAN mutations.
Keywords: versican, human, Periodontium, Dental Cementum, Wagner syndrome
Received: 25 Jul 2018;
Accepted: 22 Dec 2018.
Edited by:Musharraf Jelani, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Saudi Arabia
Reviewed by:Saadullah Khan, Kohat University of Science and Technology, Pakistan
Khitab Gul, Mohammad Ali Jinnah University, Pakistan
Copyright: © 2018 Bigoni, Neri, Scotton, Farina, Sabatelli, Chongyi, Jianguo, Falzarano, Rossi, Ognibene, Selvatici, Gualandi, Bosshardt, Perri, Campa, Brancati, Salvatore, De Stefano, Taruscio, Trombelli, Mingyan and Ferlini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Alessandra Ferlini, Unità Operativa di Genetica Medica, Dipartimento di Scienze Mediche, Università di Ferrara, Ferrara, Italy, email@example.com