Abnormal Enamel Mineralization and Hypercalcemia due to GNA11 Variants
Abstract
Abnormal enamel mineralization has been reported in genetic conditions associated with hypocalcemia but never with hypercalcemia. In the present study, we report 10 patients from 2 unrelated families in whom hypomineralized enamel co-segregated with hypercalcemia due to a complete deletion or frameshifting premature truncation (p.(Ser18Argfs*2)) of the guanine nucleotide–binding protein (G-protein) subunit α 11 ( GNA11 ) gene. Both GNA11 variants were heterozygous and predicted to cause a loss of function of Gα 11 . Multiproxy imaging analyses of naturally exfoliated primary teeth and clinically extracted permanent teeth from 2 affected patients revealed abnormal enamel mineralization, with constitutive patches of hypomineralization following no set pattern. In parallel, the study of wild-type mouse tooth germs using combined molecular and protein analyses showed Gna11 and Gα 11 protein expression in ameloblasts at the secretion and maturation stages, as well as in odontoblasts, suggesting a role for Gα 11 in tooth formation. Furthermore, the analysis of a mouse model of Familial Hypocalciuric Hypercalcemia 2 (FHH2) revealed delayed onset of enamel mineralization in the continuously growing incisors and hypomineralized enamel in both incisor and molars of heterozygous ( Gna11 Tm1b +/− ) mice, with defects that are very similar to those affecting human FHH2 teeth. In conclusion, our study reveals that abnormal enamel mineralization may occur in association with hypercalcemia due to loss-of-function GNA11 mutations, opening a new field of investigation and highlighting the need to include a dentist in the multidisciplinary team in charge of patients with monogenic calcium disorders.
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BibTeX
@article{obtel2026abnormal,
title = {{Abnormal Enamel Mineralization and Hypercalcemia due to GNA11 Variants}},
author = {N. Obtel and A. Le Cabec and A.-L. Lakhel and A. Attia and C. Andrique and F. Hermans and F. Kovaci and T.N. Nguyen and A. Chansavang and A. Percot and C. Torrens and D. Vangu and F. Vaysse and M. Gadion and F. Savagner and T. Edouard and A. Bloch-Zupan and B. Lukić and A. Rack and A. Brunelle and A. Linglart and E. Pasmant and F. Ramirez Rozzi and F.M. Hannan and T. Coradin and R.V. Thakker and J-P Bertocchio and C. Chaussain},
journal = {Journal of Dental Research},
year = {2026},
month = aug,
doi = {10.1177/00220345261470370},
url = {https://hal.science/hal-05742901v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Abnormal Enamel Mineralization and Hypercalcemia due to GNA11 Variants
AU - N. Obtel
AU - A. Le Cabec
AU - A.-L. Lakhel
AU - A. Attia
AU - C. Andrique
AU - F. Hermans
AU - F. Kovaci
AU - T.N. Nguyen
AU - A. Chansavang
AU - A. Percot
AU - C. Torrens
AU - D. Vangu
AU - F. Vaysse
AU - M. Gadion
AU - F. Savagner
AU - T. Edouard
AU - A. Bloch-Zupan
AU - B. Lukić
AU - A. Rack
AU - A. Brunelle
AU - A. Linglart
AU - E. Pasmant
AU - F. Ramirez Rozzi
AU - F.M. Hannan
AU - T. Coradin
AU - R.V. Thakker
AU - J-P Bertocchio
AU - C. Chaussain
PY - 2026
DA - 2026/08/31
JO - Journal of Dental Research
DO - 10.1177/00220345261470370
UR - https://hal.science/hal-05742901v1
AB - Abnormal enamel mineralization has been reported in genetic conditions associated with hypocalcemia but never with hypercalcemia. In the present study, we report 10 patients from 2 unrelated families in whom hypomineralized enamel co-segregated with hypercalcemia due to a complete deletion or frameshifting premature truncation (p.(Ser18Argfs*2)) of the guanine nucleotide–binding protein (G-protein) subunit α 11 ( GNA11 ) gene. Both GNA11 variants were heterozygous and predicted to cause a loss of function of Gα 11 . Multiproxy imaging analyses of naturally exfoliated primary teeth and clinically extracted permanent teeth from 2 affected patients revealed abnormal enamel mineralization, with constitutive patches of hypomineralization following no set pattern. In parallel, the study of wild-type mouse tooth germs using combined molecular and protein analyses showed Gna11 and Gα 11 protein expression in ameloblasts at the secretion and maturation stages, as well as in odontoblasts, suggesting a role for Gα 11 in tooth formation. Furthermore, the analysis of a mouse model of Familial Hypocalciuric Hypercalcemia 2 (FHH2) revealed delayed onset of enamel mineralization in the continuously growing incisors and hypomineralized enamel in both incisor and molars of heterozygous ( Gna11 Tm1b +/− ) mice, with defects that are very similar to those affecting human FHH2 teeth. In conclusion, our study reveals that abnormal enamel mineralization may occur in association with hypercalcemia due to loss-of-function GNA11 mutations, opening a new field of investigation and highlighting the need to include a dentist in the multidisciplinary team in charge of patients with monogenic calcium disorders.
SN - 0022-0345
ER -