title: Pregnancy following preimplantation genetic diagnosis for Crouzon syndrome.
abstract: Crouzon syndrome is a dominantly inherited craniosynostosis syndrome which is caused by mutations in the fibroblast growth factor receptor 2 gene (FGFR2). However, a specific point mutation in the FGFR3 gene has also been shown to result in Crouzon syndrome associated with acanthosis nigricans. We report here the first method for preimplantation genetic diagnosis (PGD) of Crouzon syndrome based on multiplex PCR amplification followed by the direct detection of the causative mutation by single-stranded conformational polymorphism (SSCP) analysis. A highly polymorphic short tandem repeat (STR) locus was simultaneously analysed as a control against some forms of contamination. The mutation, carried by the female partner, was a de-novo substitution at codon 338 of the FGFR2 gene. The couple were found to be informative at the D21S11 STR locus. Two clinical PGD cycles were performed, resulting in the biopsy of 36 blastomeres, 25 of which showed amplification at the FGFR2 locus. All of the cells showed expected genotypes at the D21S11 locus with only one incidence of allele drop-out. A total of five embryos were transferred, two in the first cycle and three in the second, resulting in a singleton pregnancy.
authors.affiliation: UCL Centre for Preimplantation Genetic Diagnosis and the Assisted Conception Unit, Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, London WC1E 6HX, UK. patrick.sleiman@ucl.ac.uk
authors.forename: P M
authors.initials: PM
authors.lastname: Abou-Sleiman
authors.forename: A
authors.initials: A
authors.lastname: Apessos
authors.forename: J C
authors.initials: JC
authors.lastname: Harper
authors.forename: P
authors.initials: P
authors.lastname: Serhal
authors.forename: J D A
authors.initials: JD
authors.lastname: Delhanty
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002891:Chromosomes, Human, Pair 21; D003394:Craniofacial Dysostosis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D020554:Sperm Injections, Intracytoplasmic; D020080:Tandem Repeat Sequences
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2