“…The amino-acid substitution at codon 9 could have effect on the signal peptide cleavage site, resulting in PTHLH loss of function ( Wang et al, 2015 ). This can lead to increased chondrocyte apoptosis and premature closure of growth plates resulting in BDE, advanced bone age and short stature like in our patients ( Reyes et al, 2020 ; Reyes et al, 2019 ). PTHR1 activates the Gsα-cAMP-PKA-PDE4D signaling pathway and mutations in other genes encoding for proteins in this pathway, namely GNAS (leading to PHP or PPHP), PRKAR1A and PDE4D (leading to acrodysostosis type 1 and 2 respectively), can also lead to BDE and short stature ( Reyes et al, 2019 ; Thomas-Teinturier et al, 2016 ).…”