Clinical Chemistry 55: 2214-2217, 2009. First published October 15, 2009; 10.1373/clinchem.2009.133298
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(Clinical Chemistry. 2009;55:2214-2217.)
© 2009 American Association for Clinical Chemistry, Inc.

Brief Communications

Amniotic Fluid Digestive Enzyme Analysis Is Useful for Identifying CFTR Gene Mutations of Unclear Significance

Florine Oca1, Sophie Dreux1, Bénédicte Gérard2, Brigitte Simon-Bouy3, Alix de Becdelièvre4, Claude Ferec5, Emmanuelle Girodon4 and Françoise Muller1,6,a

1 Biochimie-Hormonologie and 2 Biochimie Génétique, Hôpital Robert Debré, AP-HP, Paris, France; 3 SESEP, Hôpital André Mignot, Le Chesnay, France; 4 Biochimie Génétique, CHU Henri Mondor, AP-HP, and INSERM U955 équipe 11, Créteil, France; 5 Génétique, CHU Brest, Brest, France; 6 Université Paris Ile de France Ouest, Paris, France;

aaddress correspondence to this author at: Biochimie Hormonale, Hôpital Robert Debré, 48, Bd Sérurier, 75935 Paris Cedex 19, France. Fax +33-1-40-03-53-80; e-mail francoise. muller{at}rdb.aphp.fr.


Abstract

Background: The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations.

Methods: The AF-DE pattern ({gamma}-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied.

Results: Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2–4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases.

Conclusions: AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.