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Case Reports
. 1998 May 18;77(3):219-24.
doi: 10.1002/(sici)1096-8628(19980518)77:3<219::aid-ajmg6>3.0.co;2-k.

FGFR2 mutation associated with clinical manifestations consistent with Antley-Bixler syndrome

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Case Reports

FGFR2 mutation associated with clinical manifestations consistent with Antley-Bixler syndrome

K Chun et al. Am J Med Genet. .

Abstract

The Antley-Bixler syndrome (ABS) is a rare syndrome with synostosis of cranial sutures and elbow joints as minimal diagnostic criteria. The inheritance has been suggested to be autosomal recessive based on two families with sib recurrence with both sexes being affected, and two cases born to consanguineous parents. We report the first case of ABS associated with an apparent dominant de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient was found to be heterozygous for a C-->G transversion at nucleotide 1064, which predicts a Ser351Cys amino acid substitution in the IgIII domain of FGFR2. Apart from the craniosynostosis and elbow ankylosis, our patient also presented with severe spinal dysraphism, the first report of such a finding in association with ABS. This suggests that FGFR2 is expressed as early as the fourth week of embryogenesis when somite formation occurs. We propose that the Antley-Bixler syndrome is an autosomal dominant condition with possible gonadal mosaicism. Alternatively, there may be two types of ABS: an autosomal dominant form and an autosomal recessive form. In light of our findings, FGFR mutations should be looked for in other craniosynostosis patients with elbow synostosis.

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