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GENATLAS PHENOTYPE
last update : 30-01-2013
Symbol ACS1
Location 10q26.13
Name acrocephalosyndactyly type 1
Other name(s) Apert syndrome
Corresponding gene FGFR2
Main clinical features
  • craniosynostosis, midfacial hypoplasia, brachycephaly, ocular proptosis, beaked nose, high arched cleft palate, mental retardation and severe syndactyly hands/feets
  • agenesis of corpus callosum
    • Genetic determination autosomal dominant
    Function/system disorder osteo-articular
    Type disease
    Gene product
    Name fibroblast growth factor receptor 2 (FGFR2)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    other   abnormal protein/gain of function . gain-of-function substitution S252W in spermatogonia, and leading to soluble FGFR2 controling osteoblast differentiation
    unknown   abnormal protein/gain of function two prevalent activating mutations (S252W) and (P253R), respectively 63 and 37p100 of cases
    Remark(s) . interaction of FRS2 with the P253R receptor occurs exclusively at the plasma membrane, not at the vesicular membrane (PMID: 18373495))
  • S252W fibroblasts can induce osteogenic differentiation in periosteal MSCs (mesenchymal stem cells) but not in MSCs from another tissue; MSCs and fibroblasts responded differently to the pathogenic effects of the FGFR2(S252W) mutation (PMID: 22048896))
    • Genotype/Phenotype correlations
  • two heterozygous gain-of-function substitutions (S252W and P253R) in exon IIIa of fibroblast growth factor receptor 2 (FGFR2) are responsible for >98p100 of cases (PMID: 18726952))
  • Ser252Trp mutation in FGFR2 alters osteogenic potential and gene expression of cranial periosteal cells (PMID: 17622301))