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PMID: 10633130 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?

Journal of medical genetics ·Vol. 37 ·No. 1 ·2000-01-00 ·Pages 26-32

Reardon W, Smith A, Honour JW, Hindmarsh P, Das D, Rumsby G, Nelson I, Malcolm S, Adès L, Sillence D, Kumar D, DeLozier-Blanchet C, McKee S, Kelly T, McKeehan WL, Baraitser M, Winter RM

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.

MeSH Terms
Abnormalities, Drug-Induced/genetics Abnormalities, Multiple/genetics Ankle Joint/abnormalities Ankylosis/genetics Craniosynostoses/genetics Eye Abnormalities/genetics Female Fluconazole/adverse effects Genitalia, Female/abnormalities Humans Infant Karyotyping Male Pregnancy Prenatal Exposure Delayed Effects Receptor Protein-Tyrosine Kinases/genetics Receptor, Fibroblast Growth Factor, Type 2 Receptors, Fibroblast Growth Factor/genetics Sex Characteristics Syndrome
Chemicals
Receptors, Fibroblast Growth Factor Fluconazole FGFR2 protein, human Receptor Protein-Tyrosine Kinases Receptor, Fibroblast Growth Factor, Type 2
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Reardon W
Department of Clinical Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Smith A
Honour J W
Hindmarsh P
Das D
Rumsby G
Nelson I
Malcolm S
Adès L
Sillence D
Kumar D
DeLozier-Blanchet C
McKee S
Kelly T
McKeehan W L
Baraitser M
Winter R M
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Article Info
Journal
Journal of medical genetics
Abbr.
J Med Genet
ISSN
0022-2593
DOI
10.1136/jmg.37.1.26
Published
2000-01-00
Pages
26-32
Language
English
Region
England
NLM ID
2985087R
PMCID
PMC1734444
Subset
IM
External Links
PubMed source DOI: 10.1136/jmg.37.1.26 PMC Full Text View journal details
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