Prenatal Molecular Diagnosis of Inherited Cholestatic Diseases

Jung, Camille*; Driancourt, Catherine; Baussan, Christiane; Zater, Mokhtar; Hadchouel, Michelle*,†; Meunier-Rotival, Michèle; Guiochon-Mantel, Anne§; Jacquemin, Emmanuel*,†

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318036a569
Original Articles: Hepatology & Nutrition

Objectives: 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.

Patients and 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.

Author Information

*Pediatric Hepatology and National Reference Centre for Biliary Atresia

INSERM U347, E0020, and U804

Departments of Biochemistry

§Molecular Genetics, Pharmacogenetics and Hormonology, Bicêtre Hospital, University of Paris-South XI, AP-HP, Paris, France

Received 16 October, 2006

Accepted 27 December, 2006

Address correspondence and reprint requests to Prof Emmanuel Jacquemin, Hépatologie Pédiatrique, Centre de Référence National de l'Atrésie des Voies Biliaires, Centre Hospitalier Universitaire de Bicêtre, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France (e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.