The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.
Targeted sequencing of tissue from the right gluteal mass, revealed a mosaic activating FGFR1 c.1966A>G (p.Lys656Glu) mutation, absent in normal left gluteal tissue, confirming the diagnosis of encephalocraniocutaneous lipomatosis (ECCL), belonging to the family of RASopathies (including neurofibromatosis type I, Noonan syndrome, Costello syndrome), with constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, and an increased risk of developing neoplasms.
Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1.
Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling.
Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling.