One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.
Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism.
FGFR3 is expressed in the brain during development and plays a role in hippocampal formation, and FGFR3 mutations could cause cerebral malformations in hypochondroplasia.
These results together with our earlier observation that achondroplasia results from constitutive activation of the related receptor FGFR3, leads to the prediction that other malformation syndromes attributed to FGFRs, such as Pfeiffer syndrome and Thanatophoric dysplasia, also arise from constitutive receptor activation.