Novel ABCC2 mutations in a neonate with Dubin-Johnson syndrome: a case report
- 1Department of Nutrition, Baoding Hospital, Beijing Children’s Hospital Affiliated to Capital Medical University
- 2Department of Gastroenterology, Baoding Hospital, Beijing Children’s Hospital Affiliated to Capital Medical University
Abstract
Background: Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder caused by mutations in the ABCC2 gene, leading to impaired excretion of conjugated bilirubin. Neonatal or infantile onset is uncommon and easily misdiagnosed as biliary atresia or progressive familial intrahepatic cholestasis.
Case presentation: We report a female infant who presented with persistent jaundice since birth (onset in the neonatal period, ≤28 days). A definitive genetic diagnosis of Dubin-Johnson syndrome (DJS) was established at 11 months of age through next-generation sequencing. Her subsequent 5-year follow-up indicates a favorable clinical course. Laboratory tests revealed consistently normal transaminase levels with elevated total bilirubin (peak 120.3 μmol/L at 52 days), direct bilirubin (peak 61.3 μmol/L), and gamma-glutamyl transferase (88 U/L). Next-generation sequencing identified two novel compound heterozygous mutations in the ABCC2 gene: c.2443C>T (p.R815X, nonsense) inherited from the mother and c.4465_4473delinsGGCCCACAG (p.1489_1491delinsGPQ, in-frame) inherited from the father. Both mutations were classified as pathogenic/likely pathogenic according to ACMG guidelines (c.2443C>T: PVS1, PM2, PM3; c.4465_4473delinsGGCCCACAG: PM2, PM3, PM4) and have not been previously reported. Ursodeoxycholic acid therapy was administered, and bilirubin levels showed progressive decline over time; however, this improvement may also reflect the spontaneous trend toward resolution that is characteristic of the natural history of DJS.
Conclusion: This case expands the mutational spectrum of ABCC2 gene and highlights the critical role of genetic testing in early diagnosis of infantile DJS, thereby avoiding unnecessary invasive procedures. The favorable prognosis with conservative management further supports the benign nature of this condition.
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BibTeX
@article{an2026novel,
title = {{Novel ABCC2 mutations in a neonate with Dubin-Johnson syndrome: a case report}},
author = {Lijun An and Yuanda Zhang and Sisi Zhang},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1913891},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1913891/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Novel ABCC2 mutations in a neonate with Dubin-Johnson syndrome: a case report
AU - Lijun An
AU - Yuanda Zhang
AU - Sisi Zhang
PY - 2026
DA - 2026/10/15
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1913891
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1913891/full
AB - Background: Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder caused by mutations in the ABCC2 gene, leading to impaired excretion of conjugated bilirubin. Neonatal or infantile onset is uncommon and easily misdiagnosed as biliary atresia or progressive familial intrahepatic cholestasis. Case presentation: We report a female infant who presented with persistent jaundice since birth (onset in the neonatal period, ≤28 days). A definitive genetic diagnosis of Dubin-Johnson syndrome (DJS) was established at 11 months of age through next-generation sequencing. Her subsequent 5-year follow-up indicates a favorable clinical course. Laboratory tests revealed consistently normal transaminase levels with elevated total bilirubin (peak 120.3 μmol/L at 52 days), direct bilirubin (peak 61.3 μmol/L), and gamma-glutamyl transferase (88 U/L). Next-generation sequencing identified two novel compound heterozygous mutations in the ABCC2 gene: c.2443C>T (p.R815X, nonsense) inherited from the mother and c.4465_4473delinsGGCCCACAG (p.1489_1491delinsGPQ, in-frame) inherited from the father. Both mutations were classified as pathogenic/likely pathogenic according to ACMG guidelines (c.2443C>T: PVS1, PM2, PM3; c.4465_4473delinsGGCCCACAG: PM2, PM3, PM4) and have not been previously reported. Ursodeoxycholic acid therapy was administered, and bilirubin levels showed progressive decline over time; however, this improvement may also reflect the spontaneous trend toward resolution that is characteristic of the natural history of DJS. Conclusion: This case expands the mutational spectrum of ABCC2 gene and highlights the critical role of genetic testing in early diagnosis of infantile DJS, thereby avoiding unnecessary invasive procedures. The favorable prognosis with conservative management further supports the benign nature of this condition.
SN - 1664-2392
ER -