FGFR3 mutation causes abnormal membranous ossification in achondroplasia.

[achondroplasia]

FGFR 3 gain-of-function mutations lead to both chondrodysplasias and craniosynostoses . Achondroplasia (ACH ), the most frequent dwarfism , is due to an FGFR 3 -activating mutation which results in impaired endochondral ossification . The effects of the mutation on membranous ossification are unknown . Fgfr 3 (Y 367 C /+) mice mimicking ACH and craniofacial analysis of patients with ACH and FGFR 3 -related craniosynostoses provide an opportunity to address this issue . Studying the calvaria and skull base , we observed abnormal cartilage and premature fusion of the synchondroses leading to modifications of foramen magnum shape and size in Fgfr 3 (Y 367 C /+) mice , ACH and FGFR 3 -related craniosynostoses patients . Partial premature fusion of the coronal sutures and non-ossified gaps in frontal bones were also present in Fgfr 3 (Y 367 C /+) mice and ACH patients . Our data provide strong support that not only endochondral ossification but also membranous ossification is severely affected in ACH . Demonstration of the impact of FGFR 3 mutations on craniofacial development should initiate novel pharmacological and surgical therapeutic approaches .

Diseases
Validation

Diseases presenting "dwarfism" symptom

achondroplasia

gm1 gangliosidosis

kabuki syndrome

lamellar ichthyosis

oculocutaneous albinism

oligodontia

proteus syndrome

This symptom has already been validated