ANALYSIS OF PHENOTYPIC FEATURES AND FGFR2 MUTATIONS IN APERT SYNDROME

A phenotypic and genotypic survey was conducted on 36 Apert syndrome p atients. In all but one patient, an FGFR2 mutation, either S252W or P2 53R, was found in exon IIIa (exon U or 7). The frequency was 71% and 2 6%, for the mutations S252W and P253R, respectively. These mutations o ccur in the linker region between immunoglobulin-like domains II and I ii, which are involved in activation of the receptor by ligand binding and dimerization. The fact that one patient did not have a mutation i n the same exon suggests further genetic heterogeneity in Apert syndro me. The frequencies of occurrence or means for measurements of 29 diff erent clinical features (including severity of craniofacial features, syndactyly of the hands and feet, and multisystem involvement) were de termined for all patients and for the two subgroups defined by their m utations. Comparison between the subgroups for the different clinical features was performed and suggested no statistically significant diff erences, These results are not unexpected, because the two common muta tions for Apert syndrome alter FGFR2 at adjacent amino acids that are likely to have similar biological, and therefore phenotypic, consequen ces.