A false positive newborn screening result due to a complex allele carrying two frequent CF-causing variants.
The detection of two frequent CFTR disease-causing variations in the context of a newborn screening program (NBS) usually leads to the diagnosis of cystic fibrosis (CF) and a relevant genetic counseling in the family. In the present study, CF-causing variants p.Phe508del (F508del) and c.3140-26A>G (3272-26A>G) were identified on a neonate with positive ImmunoReactive Trypsinogen test by the Elucigene™ CF30 kit. The CF diagnosis initially suggested, despite three inconclusive Sweat Chloride Tests (SCT), was finally ruled out after the familial segregation study combined with a negative SCT. Haplotype studies, based on the comparison of 80 p.Phe508del haplotypes, suggested a probable de novo occurrence of c.3140-26A>G on the p.Phe508del ancestral allele in this family. This false positive case emphasizes the importance of SCT in the NBS strategy. Moreover, it raises the need for familial segregation studies in CF and in overall molecular diagnosis strategy of autosomal recessive diseases.
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France. Electronic address: anne.bergougnoux@inserm.fr.
Anne
A
Bergougnoux
Service de Génétique Médicale, Hôpital L'Archet 2, 06200 Nice, France.
Amandine
A
Boureau-Wirth
Service de Génétique Médicale, Hôpital L'Archet 2, 06200 Nice, France.
Cécile
C
Rouzier
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France.
Jean-Pierre
JP
Altieri
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France.
Fanny
F
Verneau
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France.
Lise
L
Larrieu
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France; Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, EA 7402, Université de Montpellier, 34000 Montpellier Cedex 5, France.
Michel
M
Koenig
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France; Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, EA 7402, Université de Montpellier, 34000 Montpellier Cedex 5, France.
Mireille
M
Claustres
Laboratoire de Génétique Moléculaire, CHRU Montpellier, 34093 Montpellier Cedex 5, France; Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, EA 7402, Université de Montpellier, 34000 Montpellier Cedex 5, France.
Caroline
C
Raynal
D000483:Alleles; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D005190:Family; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D007159:Immunologic Tests / Q000379:methods; D007231:Infant, Newborn; D008487:Medical History Taking / Q000379:methods; D015997:Neonatal Screening / Q000379:methods*; D013542:Sweat / Q000378:metabolism*; D014362:Trypsinogen / Q000032:analysis*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen
CFTR gene; Complex allele; Cystic fibrosis; False positive; Newborn screening