AUTHOR=Bigoni Stefania , Neri Marcella , Scotton Chiara , Farina Roberto , Sabatelli Patrizia , Jiang Chongyi , Zhang Jianguo , Falzarano Maria Sofia , Rossi Rachele , Ognibene Davide , Selvatici Rita , Gualandi Francesca , Bosshardt Dieter , Perri Paolo , Campa Claudio , Brancati Francesco , Salvatore Marco , De Stefano Maria Chiara , Taruscio Domenica , Trombelli Leonardo , Fang Mingyan , Ferlini Alessandra TITLE=Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family JOURNAL=Frontiers in Genetics VOLUME=Volume 9 - 2018 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00723 DOI=10.3389/fgene.2018.00723 ISSN=1664-8021 ABSTRACT=

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.