title: Analysis of phenotypic features and FGFR2 mutations in Apert syndrome.
abstract: A phenotypic and genotypic survey was conducted on 36 Apert syndrome patients. In all but one patient, an FGFR2 mutation, either S252W or P253R, was found in exon IIIa (exon U or 7). The frequency was 71% and 26%, for the mutations S252W and P253R, respectively. These mutations occur in the linker region between immunoglobulin-like domains II and III, which are involved in activation of the receptor by ligand binding and dimerization. The fact that one patient did not have a mutation in the same exon suggests further genetic heterogeneity in Apert syndrome. The frequencies of occurrence or means for measurements of 29 different clinical features (including severity of craniofacial features, syndactyly of the hands and feet, and multisystem involvement) were determined for all patients and for the two subgroups defined by their mutations. Comparison between the subgroups for the different clinical features was performed and suggested no statistically significant differences. These results are not unexpected, because the two common mutations for Apert syndrome alter FGFR2 at adjacent amino acids that are likely to have similar biological, and therefore phenotypic, consequences.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Park
authors.forename: C
authors.initials: C
authors.lastname: Theda
authors.forename: N E
authors.initials: NE
authors.lastname: Maestri
authors.forename: G A
authors.initials: GA
authors.lastname: Meyers
authors.forename: J S
authors.initials: JS
authors.lastname: Fryburg
authors.forename: C
authors.initials: C
authors.lastname: Dufresne
authors.forename: M M
authors.initials: MM
authors.lastname: Cohen
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype