Related Experiment Videos
Pfeiffer syndrome caused by haploinsufficient mutation of FGFR2
1The Institute of DNA Medicine, Department of Plastic and Reconstructive Surgery, The Jikei University School of Medicine, Tokyo, Japan. marit@jikei.ac.jp
Abstract:
Mutations of the fibroblast growth factor receptors (FGFRs) cause several dominantly inherited congenital skeletal disorders and syndromes. Recently, these mutations have been suggested to cause either ligand-independent activation of the receptor or a dominant negative inactivation. The analysis of two Japanese patients with Pfeiffer syndrome and postaxial polydactyly of the hand now shows that both carried the same 1119-2A-to-G transition of the FGFR2 gene and this nonsense mutation caused skipping of exon 9(B) and haploinsufficiency of FGFR2.
Insights
Fibroblast growth factor receptor 2 (FGFR2) gene mutations cause skeletal disorders. A specific nonsense mutation in Japanese patients led to exon skipping and FGFR2 haploinsufficiency, explaining Pfeiffer syndrome.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Fibroblast growth factor receptors (FGFRs) mutations are linked to congenital skeletal disorders.
- These mutations may result in ligand-independent activation or dominant negative inactivation of the receptor.
Observation:
- Two Japanese patients with Pfeiffer syndrome and postaxial polydactyly were analyzed.
- Both patients shared a specific 1119-2A-to-G transition in the FGFR2 gene.
Findings:
- The identified nonsense mutation in FGFR2 caused skipping of exon 9(B).
- This exon skipping resulted in haploinsufficiency of FGFR2, a critical protein in skeletal development.
Implications:
- This finding clarifies the molecular mechanism underlying Pfeiffer syndrome in these patients.
- Understanding FGFR2 haploinsufficiency provides insights into skeletal development and related genetic disorders.