2011 Skeletal Dysplasia Course

Feb 15, 2017

A new skeletal dysplasia with immune deficiency and developmental delay associated with mutations in EXTL3


Skeletal dysplasia, severe immune deficiency (presenting in the newborn as Omenn syndrome), and developmental delay: this newly recognized condition is caused by mutations in EXTL3, an enzyme responsible for the synthesis of heparan sulfate. 

Category: General
Posted by: asuperti
As nicely shown in the recent JEM paper, the pathogenesis involves a perturbation of FGF signalling. This explains some sinilkarities of the condition with FGFR3 dysplasias. This work was initiated by the clinical observation of affected sibs at the Gaslini Hospital in Genova, Italy, followed by the genetic workup and elucidation in Lausanne. The Boston group studied the pathogenesis in lymphoctes and in a fish model, and a further affected case study from San Francisco rounded up the work. The biological insights on the role of heparan sulfate modulation on FGF/FGFR signalling in the development of bone, brain and thymus are important, as are the clinical implications for diagnosis, counselling, and therapeutic approaches to the immunodeficiency.