Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family

Stefania Bigoni, Marcella Neri, Chiara Scotton, Roberto Farina, Patrizia Sabatelli, Chongyi Jiang, Jianguo Zhang, Maria Sofia Falzarano, Rachele Rossi, Davide Ognibene, Rita Selvatici, Francesca Gualandi, Dieter Bosshardt, Paolo Perri, Claudio Campa, Francesco Brancati, Marco Salvatore, Maria Chiara De Stefano, Domenica Taruscio, Leonardo TrombelliMingyan Fang, Alessandra Ferlini

Research output: Contribution to journalArticlepeer-review


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 sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations.
Original languageEnglish
JournalFrontiers in Genetics
Publication statusPublished - Jan 21 2019


  • versican
  • human
  • periodontium
  • dental cementum
  • Wagner syndrome


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