Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.
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.
Oca
Florine
F
Biochimie-Hormonologie, Hôpital Robert Debré, AP-HP, Paris, France.
Dreux
Sophie
S
Gérard
Bénédicte
B
Simon-Bouy
Brigitte
B
de Becdelièvre
Alix
A
Ferec
Claude
C
Girodon
Emmanuelle
E
Muller
Françoise
F
D000469:Alkaline Phosphatase / Q000032:analysis*; D000653:Amniotic Fluid / Q000201:enzymology*; D000951:Antigens, Neoplasm / Q000032:analysis*; D018826:CD13 Antigens / Q000032:analysis*; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D016208:Databases, Factual; D005333:Fetus; D058851:GPI-Linked Proteins; D006801:Humans; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis; D009154:Mutation; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D005723:gamma-Glutamyltransferase / Q000032:analysis*
D000951:Antigens, Neoplasm; C505032:CFTR protein, human; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005723:gamma-Glutamyltransferase; C063088:ALPI protein, human; D000469:Alkaline Phosphatase; D018826:CD13 Antigens