In this communication, we report the identification of a mosaic R248C missense mutation in the IgII-III linker region of the gene encoding the fibroblast growth factor receptor-3 (FGFR3), in an individual who manifests a skeletal dysplasia and epidermal hyperplasia.
We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1).
Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.
Other mutations within the FGFR3 tyrosine kinase domain (e.g., C1620A or C1620G [both resulting in Asn540Lys]) are known to cause hypochondroplasia, a relatively common but milder skeletal dysplasia.
A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms.
Activating mutations of the FGFR3 gene lead to craniosynostosis and multiple types of skeletal dysplasia with varying degrees of severity: thanatophoric dysplasia (TD), achondroplasia and hypochondroplasia.
We describe the first case of protein-losing enteropathy in a pediatric patient, with severe skeletal dysplasia consistent with thanatophoric dysplasia type I and DNA analysis that revealed a c.1949A>T (p.Lys650Met) in exon 15 of the FGFR3 gene.
Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth.
Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia due to mutations causing haploinsufficiency of RUNX2, an osteoblast transcription factor specific for bone and cartilage.
Cleidocranial dysplasia (CCD) is a rare autosomal-dominantly inherited skeletal dysplasia that is predominantly associated with heterozygous mutations of RUNX2.
Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3.