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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00723

Homozygous recessive Versican missense variation is associated with early teeth loss in a Pakistani family

Stefania Bigoni1, Marcella Neri1, Chiara Scotton1,  Roberto Farina2,  Patrizia Sabatelli3, Jiang Chongyi4, Zhang Jianguo4, Maria Sofia Falzarano1, Rachele Rossi1, Davide Ognibene1,  Rita Selvatici1, Francesca Gualandi1,  Dieter Bosshardt5,  Paolo Perri6, Claudio Campa6,  Francesco Brancati7, Marco Salvatore8,  Maria Chiara De Stefano8, Domenica Taruscio8, Leonardo Trombelli2,  Fang Mingyan4 and  Alessandra Ferlini1, 9*
  • 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,