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Updated: Jul 15, 2026
Isolation of Neonatal Extrahepatic Cholangiocytes
Published on: June 5, 2014
Prenatal molecular diagnosis of inherited cholestatic diseases
Camille Jung1, Catherine Driancourt, Christiane Baussan
1Pediatric Hepatology and National Reference Centre for Biliary Atresia, Bicêtre Hospital, University of Paris-South XI, AP-HP, Paris, France.
Insights
Prenatal diagnosis for progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome using DNA testing is reliable. Molecular results accurately predicted infant health outcomes, enabling informed family planning.
Area of Science:
- Medical Genetics
- Pediatric Hepatology
- Prenatal Diagnosis
Background:
- Progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome frequently cause childhood end-stage liver disease.
- Early diagnosis is crucial for managing these severe pediatric liver conditions.
Purpose of the Study:
- To evaluate the reliability of DNA-based prenatal diagnosis for PFIC (types 1-3) and Alagille syndrome.
- To correlate molecular prenatal findings with postnatal clinical outcomes.
Main Methods:
- Conducted molecular antenatal diagnoses in 3 PFIC families and 11 Alagille syndrome families.
- Utilized DNA from chorionic villus or cultured amniocyte samples for genetic analysis.
- Analyzed mutations in ATP8B1, ABCB11, ABCB4 (PFIC) and JAG1 (Alagille syndrome) genes.
Main Results:
- All PFIC-affected fetuses were heterozygous for relevant gene mutations; pregnancies continued with healthy outcomes for most infants.
- One premature infant with an ABCB4 mutation experienced transient neonatal cholestasis.
- In Alagille syndrome, de novo mutations were absent in fetuses, while familial mutations occurred in 40%; 3 of 4 pregnancies with mutated fetuses were terminated.
Conclusions:
- DNA-based prenatal diagnosis for PFIC1-3 and Alagille syndrome is a dependable tool.
- Molecular prenatal data strongly correlate with clinical outcomes, supporting its use in genetic counseling and management.
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.
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