Notable contribution of large CFTR gene rearrangements to the diagnosis of cystic fibrosis in fetuses with bowel anomalies.
Grade III fetal bowel hyperechogenicity and/or loop dilatation observed at the second trimester of pregnancy can be due to several disease conditions, including cystic fibrosis (CF). Screening for frequent CF mutations is performed as a first step and, in certain situations, such as when a frequent CF mutation is found in the fetus, the increased risk of CF justifies an in-depth study of the second allele. To determine the contribution of large CFTR gene rearrangements in such cases, detected using a semiquantitative fluorescent multiplex PCR (QFM-PCR) assay, we collated data on 669 referrals related to suspicion of CF in fetuses from 1998 to 2009. Deletions were found in 5/70 cases in which QFM-PCR was applied, dele19, dele22_23, dele2_6b, dele14b_15 and dele6a_6b, of which the last three remain undescribed. In 3/5 cases, hyperechogenicity was associated with dilatation and/or gallbladder anomalies. Of the total cases of CF recognized in the subgroup of first-hand referrals, deletions represent 16.7% of CF alleles. Our study thus strengthens the need to consider large CFTR gene rearrangements in the diagnosis strategy of fetal bowel anomalies, in particular in the presence of multiple anomalies.
Service de Biochimie-Génétique et Inserm U955 Equipe 11, Groupe Hospitalier Henri Mondor-Albert Chenevier, APHP, Créteil, France.
Alix
A
de Becdelièvre
Catherine
C
Costa
Annick
A
LeFloch
Marie
M
Legendre
Jean-Marie
JM
Jouannic
Jacqueline
J
Vigneron
Jean-Luc
JL
Bresson
Stéphanie
S
Gobin
Josiane
J
Martin
Michel
M
Goossens
Emmanuelle
E
Girodon
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D002869:Chromosome Aberrations; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D058535:Echogenic Bowel / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D005704:Gallbladder / Q000002:abnormalities; D015321:Gene Rearrangement; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D007422:Intestines / Q000196:embryology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D017384:Sequence Deletion
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator