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.

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

Bigoni, Stefania
Co-primo
Membro del Collaboration Group
;
Neri, Marcella
Co-primo
Membro del Collaboration Group
;
Scotton, Chiara
Co-primo
Membro del Collaboration Group
;
Farina, Roberto
Secondo
Membro del Collaboration Group
;
Sabatelli, Patrizia
Membro del Collaboration Group
;
Falzarano, Maria Sofia
Membro del Collaboration Group
;
Rossi, Rachele
Membro del Collaboration Group
;
Ognibene, Davide
Membro del Collaboration Group
;
Selvatici, Rita
Membro del Collaboration Group
;
Gualandi, Francesca
Membro del Collaboration Group
;
Perri, Paolo
Membro del Collaboration Group
;
Campa, Claudio
Membro del Collaboration Group
;
Trombelli, Leonardo
Conceptualization
;
Ferlini, Alessandra
Ultimo
Conceptualization
2019

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.
2019
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
File in questo prodotto:
File Dimensione Formato  
Bigoni et al 2019.pdf

accesso aperto

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: Creative commons
Dimensione 3.24 MB
Formato Adobe PDF
3.24 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2400215
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact