title: Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?
abstract: The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.
authors.affiliation: Department of Clinical Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: W
authors.initials: W
authors.lastname: Reardon
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: J W
authors.initials: JW
authors.lastname: Honour
authors.forename: P
authors.initials: P
authors.lastname: Hindmarsh
authors.forename: D
authors.initials: D
authors.lastname: Das
authors.forename: G
authors.initials: G
authors.lastname: Rumsby
authors.forename: I
authors.initials: I
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: L
authors.initials: L
authors.lastname: Adès
authors.forename: D
authors.initials: D
authors.lastname: Sillence
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.forename: C
authors.initials: C
authors.lastname: DeLozier-Blanchet
authors.forename: S
authors.initials: S
authors.lastname: McKee
authors.forename: T
authors.initials: T
authors.lastname: Kelly
authors.forename: W L
authors.initials: WL
authors.lastname: McKeehan
authors.forename: M
authors.initials: M
authors.lastname: Baraitser
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000235:genetics; D000015:Abnormalities, Multiple / Q000235:genetics*; D000843:Ankle Joint / Q000002:abnormalities; D000844:Ankylosis / Q000235:genetics; D003398:Craniosynostoses / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D015725:Fluconazole / Q000009:adverse effects; D005836:Genitalia, Female / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012727:Sex Characteristics; D013577:Syndrome
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D015725:Fluconazole; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2