Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD).
Pathogenic allelic variants in the fibroblast growth factor receptor 3 (FGFR3) gene have been associated with a number of phenotypes including achondroplasia, hypochondroplasia, thanatophoric dysplasia, Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome), and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans).
Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type.
A group of unrelated patients (n=82), characterized by short stature, dysmorphology and X-ray abnormalities, of which mucopolysacharidoses, GM1 gangliosidosis, mucolipidosis type II/III and achondroplasia owing to FGFR3G380R mutation had been excluded, were recruited in this study.
Gain-of-function mutations in the FGFR3 gene result in chondrodysplasias which include achondroplasia (ACH), the most common form of dwarfism, in which skull, appendicular and axial skeletons are affected.
Recently it has been demonstrated that FGFR3 mutations affect not only endochondral ossification but also membranous ossification, providing new explanations for the craniofacial hallmarks in achondroplasia.
FGFR3 is a negative regulator of chondrogenesis and multiple mutations with constitutive activity of FGFR3 result in achondroplasia, one of the most common dwarfisms in humans, but the molecular mechanism remains elusive.
Gain-of-function mutations in fibroblast growth factor receptor-3 (FGFR3) lead to several types of human skeletal dysplasia syndromes including achondroplasia, hypochondroplasia and thanatophoric dysplasia (TD).