title: Comprehensive description of CFTR genotypes and ultrasound patterns in 694 cases of fetal bowel anomalies: a revised strategy.
abstract: Fetal bowel anomalies may reveal cystic fibrosis (CF) and the search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the diagnostic investigations in such pregnancies, according to European recommendations. We report on our 18-year experience to document comprehensive CFTR genotypes and correlations with ultrasound patterns in a series of 694 cases of fetal bowel anomalies. CFTR gene analysis was performed in a multistep process, including search for frequent mutations in the parents and subsequent in-depth search for rare mutations, depending on the context. Ultrasound patterns were correlated with the genotypes. Cases were distinguished according to whether they had been referred directly to our laboratory or after an initial testing in another laboratory. A total of 30 CF fetuses and 8 cases compatible with CFTR-related disorders were identified. CFTR rearrangements were found in 5/30 CF fetuses. 21.2% of fetuses carrying a frequent mutation had a second rare mutation, indicative of CF. The frequency of CF among fetuses with no frequent mutation was 0.43%. Correlation with ultrasound patterns revealed a significant frequency of multiple bowel anomalies in CF fetuses. The results emphasize the need to search for rearrangements in the diagnosis strategy of fetal bowel anomalies. The diagnostic value of ultrasound patterns combining hyperechogenic bowel, loop dilatation and/or non-visualized gallbladder reveals a need to revise current strategies and to offer extensive CFTR gene testing when the triad is diagnosed, even when no frequent mutation is found in the first-step analysis.
authors.affiliation: Service de Biochimie-Génétique, APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier, UF de Génétique, Créteil, 94010, France.
authors.forename: Alix
authors.initials: A
authors.lastname: de Becdelièvre
authors.forename: Catherine
authors.initials: C
authors.lastname: Costa
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Jouannic
authors.forename: Annick
authors.initials: A
authors.lastname: LeFloch
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Josiane
authors.initials: J
authors.lastname: Martin
authors.forename: Rachel
authors.initials: R
authors.lastname: Médina
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boissier
authors.forename: Christine
authors.initials: C
authors.lastname: Gameiro
authors.forename: Françoise
authors.initials: F
authors.lastname: Muller
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Corinne
authors.initials: C
authors.lastname: Alberti
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D058535:Echogenic Bowel / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D016216:Ultrasonography, Prenatal
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator