Co-existence of ABCB11 and DCDC2 disease: Infantile cholestasis requires both next-generation sequencing and clinical-histopathologic correlation

Eur J Hum Genet. 2020 Jun;28(6):840-844. doi: 10.1038/s41431-020-0613-0. Epub 2020 Mar 20.

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.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / metabolism
  • Bile Ducts / metabolism
  • Bile Ducts / pathology
  • Child, Preschool
  • Cholangitis, Sclerosing / complications
  • Cholangitis, Sclerosing / genetics*
  • Cholangitis, Sclerosing / pathology
  • Cholestasis / complications
  • Cholestasis / genetics*
  • Cholestasis / pathology
  • Cytodiagnosis / methods
  • Diagnosis, Differential
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Sequence Analysis, DNA / methods

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • DCDC2 protein, human
  • Microtubule-Associated Proteins