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, StefaniaCo-primo
Membro del Collaboration Group
;Neri, MarcellaCo-primo
Membro del Collaboration Group
;Scotton, ChiaraCo-primo
Membro del Collaboration Group
;Farina, RobertoSecondo
Membro del Collaboration Group
;Sabatelli, PatriziaMembro del Collaboration Group
;Falzarano, Maria SofiaMembro del Collaboration Group
;Rossi, RacheleMembro del Collaboration Group
;Ognibene, DavideMembro del Collaboration Group
;Selvatici, RitaMembro del Collaboration Group
;Gualandi, FrancescaMembro del Collaboration Group
;Perri, PaoloMembro del Collaboration Group
;Campa, ClaudioMembro del Collaboration Group
;Trombelli, LeonardoConceptualization
;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.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 SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.