Activating mutations of FGFR3, a negative regulator of bone growth, are well known to cause a variety of short-limbed bone dysplasias and craniosynostosis syndromes.
Among them, novel variants causative of familial thrombocytopenia, sclerosis bone dysplasia and the first homozygous loss-of-function mutation in FGFR3 in human causing severe skeletal deformities, tall stature and hearing impairment were identified.
Mice heterozygous for the mutation ( Fgfr3(TD/+) ) expressed the mutant allele at approximately 20% of the wild-type level and exhibited a mild bone dysplasia.
Most reported mutations in the FGFR3 gene are dominant activating mutations that cause a variety of short-limbed bone dysplasias including achondroplasia and syndromic craniosynostosis.
The missense mutation is notable because D(403) is strictly conserved among FAM20A homologues, and the corresponding defect in FAM20C caused osteosclerotic bone dysplasia and a loss of kinase activity.
In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology.
Depletion of the gene LEMD3 encoding MAN1 leads to developmental anomalies in mice, and heterozygous loss-of-function mutations in LEMD3 in humans cause sclerosing bone dysplasia.
Camurati-Engelmann disease (CED) [OMIM 131300] is an autosomal dominant sclerosing bone dysplasia recently ascribed to mutations of the transforming growth factor (TGF-beta1) gene on chromosome 19q13.1-q13.3.
In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology.
Camurati-Engelmann disease (CED) is a rare form of progressive bone dysplasia due to mutations in the transforming factor gene TGFB1 on chromosome 19q13.1-q13.3.
The findings demonstrate that mutations in TRPV4 produce a phenotypic spectrum of skeletal dysplasias from the mild autosomal-dominant brachyolmia to SMDK to autosomal-dominant metatropic dysplasia, suggesting that these disorders should be grouped into a new bone dysplasia family.
Thus, in addition to Greenberg dysplasia (a perinatal lethal disorder), homozygosity or compound heterozygosity of mutations in LBR can result in a mild, spontaneously regressing bone dysplasia.
Osteodysplasty (Melnick-Needles syndrome, MNS), a severe bone dysplasia with presumed autosomal dominant inheritance, has now been described in 24 individuals, with a predominance of females (21:3).
In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology.
We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connective tissue, manifesting as early-onset joint hypermobility, joint contractures, muscle weakness and bone dysplasia as well as high myopia, with evidence of clinical improvement of motor function over time in the surviving patient.