The fibroblast growth factor receptor 2 p.Ala172Phe mutation in Pfeiffer syndrome--history repeating itself.

Am J Med Genet A 2013 May 26;161A(5):1158-63. Epub 2013 Mar 26.

Department of Plastic Surgery, John Radcliffe Hospital, Oxford, UK.

Pfeiffer syndrome is an autosomal dominant condition classically combining craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a small number of cases can be attributed to mutations outside this region of the protein. A mild form of Pfeiffer syndrome can rarely be caused by a specific mutation in FGFR1. We report on the clinical and genetic findings in a three generation British family with Pfeiffer syndrome caused by a heterozygous missense mutation, p.Ala172Phe, located in the IgII domain of FGFR2. This is the first reported case of this particular mutation since Pfeiffer's index case, originally described in a German family in 1964, on which basis the syndrome was eponymously named. Genetic analysis demonstrated the two families to be unrelated. Similarities in phenotypes between the two families are discussed. Independent genetic origins, but phenotypic similarities in the two families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation.

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http://dx.doi.org/10.1002/ajmg.a.35842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652025PMC
May 2013
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References

(Supplied by CrossRef)
Roentgenological skull measurements and their diagnostic applications
Haas et al.
Am J Roentgenol Radium Ther Nucl Med 1952
Integrating common and rare genetic variation in diverse human populations
International HapMap 3 Consortium et al.
Nature 2010
Craniosynostosis
Johnson et al.
Eur J Hum Genet 2011

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