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Isolation of Neonatal Extrahepatic Cholangiocytes
Published on: June 5, 2014
Co-existence of ABCB11 and DCDC2 disease: Infantile cholestasis requires both next-generation sequencing and
Georg-Friedrich Vogel1, Elisabeth Maurer2, Andreas Entenmann1
1Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria.
Insights
Neonatal cholestasis in a boy was linked to a rare ABCB11 gene variant and DCDC2 gene variant, highlighting the need for integrated diagnostics. Early liver failure and specific histological findings guided the genetic investigation.
Area of Science:
- Genetics
- Hepatology
- Developmental Biology
Background:
- Neonatal cholestasis is a complex condition often requiring genetic investigation.
- Elevated gamma-glutamyl transpeptidase (GGT) and conjugated hyperbilirubinemia are key indicators.
- ABCB4 and ABCB11 gene mutations are known causes of inherited liver diseases.
Observation:
- A male infant presented with early-onset conjugated hyperbilirubinemia and liver failure.
- Initial suspicion of ABCB4 disease was not confirmed by genetic testing.
- Histopathology revealed intralobular cholestasis, sclerosing cholangiopathy, and ductal-plate malformation.
Findings:
- Homozygosity for a functional variant in the ABCB11 gene (c.1213 T>C) was identified.
- Absence of primary cilia protein DCDC2 (doublecortin domain containing 2) expression was noted.
- Homozygosity for a splice-site variant in the DCDC2 gene (c.294-2A>G) was confirmed.
Implications:
- This case highlights the co-occurrence of ABCB11 and DCDC2 related diseases in neonatal cholestasis.
- Accurate diagnosis requires integrating clinical presentation, liver histology, and comprehensive genetic analysis.
- Understanding these genetic interactions is crucial for diagnosing and managing rare liver disorders.
Abstract:
A boy exhibiting conjugated hyperbilirubinemia from birth, with elevated serum gamma-glutamyl transpeptidase activity (GGT), developed liver failure unusually early (7mo); GGT concomitantly normalized. ABCB4 disease was suspected, but no ABCB4 lesion was found. The boy was instead homozygous for ABCB11 variant c.1213 T>C (p.(Cys405Arg)), which is predicted to affect protein function. Both ABCB4 and ABCB11 were normally expressed in the explanted liver, with intralobular cholestasis; however, large-duct sclerosing cholangiopathy and ductal-plate malformation also were present. The primary-cilium constituent doublecortin domain containing 2 (DCDC2) was not expressed. Co-existence of ABCB11 disease and DCDC2 disease was proposed. Further testing identified homozygosity for the canonical-receptor splice-site variant c.294-2A>G (p.?) in DCDC2. Our report emphasizes the need to integrate clinical, histological, and genetic data in patients with neonatal cholestasis.
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