Mutational identification of fibroblast growth factor receptor 1 and fibroblast growth factor receptor 2 genes in craniosynostosis in Indian population.
We report a four-generation family with an FGFR1 P252R mutation, who have typical hand and feet skeletal features of Pfeiffer syndrome without craniofacial involvement.
However, unlike the Apert syndrome Pro253Arg FGFR2c mutant, neither the Pfeiffer syndromePro250Arg FGFR1c mutant nor the Muenke syndrome Pro250Arg FGFR3c mutant bound appreciably to FGF7 or FGF10.
However, unlike the Apert syndrome Pro253Arg FGFR2c mutant, neither the Pfeiffer syndromePro250Arg FGFR1c mutant nor the Muenke syndrome Pro250Arg FGFR3c mutant bound appreciably to FGF7 or FGF10.
We report four new affected families showing an FGFR1 P252R mutation and emphasize the characteristic malformations of the feet in this form of Pfeiffer syndrome.
In this paper the expression of FGFR1, the IgIIIa/c and IgIIIa/b isoforms of FGFR2, and FGFR3 is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues.
Molecular analysis of her fibroblast growth factor receptor 1 gene (FGFR1) identified a heterozygous P252R missense mutation, previously only reported with FGFR1-Pfeiffer syndrome like manifestations.
Molecular analysis of her fibroblast growth factor receptor 1 gene (FGFR1) identified a heterozygous P252R missense mutation, previously only reported with FGFR1-Pfeiffer syndrome like manifestations.
These studies provide direct genetic evidence that the Pro252Arg mutation in FGFR1 causes human Pfeiffer syndrome and uncovers a molecular mechanism in which Fgf/Fgfr1 signals regulate intramembraneous bone formation by modulating Cbfa1 expression.
These studies provide direct genetic evidence that the Pro252Arg mutation in FGFR1 causes human Pfeiffer syndrome and uncovers a molecular mechanism in which Fgf/Fgfr1 signals regulate intramembraneous bone formation by modulating Cbfa1 expression.
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.
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.
Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each.