Prenatal molecular diagnosis of inherited cholestatic diseases.
OBJECTIVE
Progressive familial intrahepatic cholestasis (PFIC) and to a lesser extent, Alagille syndrome, often lead to end-stage liver disease during childhood. We report our experience of DNA-based prenatal diagnosis of PFIC1-3 and Alagille syndrome.


METHODS
Four molecular antenatal diagnoses were performed in 3 PFIC families and 17 in 11 Alagille syndrome families. DNA was isolated from chorionic villus or cultured amniocyte samples from women, without pregnancy complications.


RESULTS
All four foetuses with a family history of PFIC1, 2, or 3 were heterozygous for an ATP8B1, ABCB11, or ABCB4 mutation and pregnancies were continued. Three of the infants were healthy after birth, and 1 premature infant, who had an ABCB4 mutation, experienced transient neonatal cholestasis. Among the families with a history of de novo JAG1 mutation, none of the foetuses was mutated, versus 40% of those with a history of familial mutation. Of 4 pregnant women with a JAG1-mutated foetus, 3 cut short their pregnancy and 1 gave birth to a child with overt Alagille syndrome.


CONCLUSIONS
Molecular antenatal diagnosis of PFIC1-3 and Alagille syndrome is reliable because clinical outcome after birth corresponded to molecular foetal data.
Jung
Camille
C
Pediatric Hepatology and National Reference Centre for Biliary Atresia, Bicêtre Hospital, University of Paris-South XI, AP-HP, Paris, France.
Driancourt
Catherine
C
Baussan
Christiane
C
Zater
Mokhtar
M
Hadchouel
Michelle
M
Meunier-Rotival
Michèle
M
Guiochon-Mantel
Anne
A
Jacquemin
Emmanuel
E
D016738:Alagille Syndrome / Q000175:diagnosis / Q000235:genetics; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000235:genetics*; D015193:Chorionic Villi Sampling; D004247:DNA / Q000032:analysis; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D009154:Mutation; D011247:Pregnancy
D004247:DNA