Neonatal sclerosing cholangitis with novel mutations in DCDC2 (doublecortin domain-containing protein 2) in Chinese children

Xia Wei; Yuan Fang; Jian-She Wang; Yi-Zhen Wang; Yuan Zhang; Kuerbanjiang Abuduxikuer; Lian Chen

doi:10.3389/fped.2023.1094895

Neonatal sclerosing cholangitis with novel mutations in DCDC2 (doublecortin domain-containing protein 2) in Chinese children

Front Pediatr. 2023 Feb 3:11:1094895. doi: 10.3389/fped.2023.1094895. eCollection 2023.

Authors

Xia Wei¹, Yuan Fang¹, Jian-She Wang², Yi-Zhen Wang¹, Yuan Zhang³, Kuerbanjiang Abuduxikuer², Lian Chen⁴

Affiliations

¹ Department of Pathology, Anhui Provincial Children's Hospital, Hefei, China.
² Department of Hepatology, Children's Hospital of Fudan University, Shanghai, China.
³ Department of Ultrasound, Children's Hospital of Fudan University, Shanghai, China.
⁴ Department of Pathology, Children's Hospital of Fudan University, Shanghai, China.

Abstract

Background: Neonatal sclerosing cholangitis (NSC) is a rare and severe autosomal recessive inherited liver disease with mutations in DCDC2, commonly requiring liver transplantation (LT) for decompensated biliary cirrhosis in childhood.

Methods: The information of four Chinese patients with NSC caused by mutations in DCDC2 from Children's Hospital of Fudan University were gathered. The four patients' clinicopathological and molecular features were summarized by clinical data, liver biopsy, immunohistochemical, and molecular genetic analysis.

Results: All patients presented with jaundice, hepatosplenomegaly, hyperbilirubinemia and bile embolism, and high serum γ-glutamyl transferase activity (GGT). Liver biopsies revealed varying degrees of bile duct hyperplasia, portal-tract inflammation, and/or fibrosis. Whole-exome sequencing (WES) found novel heterozygous variants of c.1024-1G > T /p.? and c.544G > A /p. Gly182Arg in the DCDC2.

Conclusion: This study expands the genetic spectrum of DCDC2 in NSC.

Keywords: DCDC2; biliary cirrhosis; ciliopathy; neonatal sclerosing cholangitis; novel mutations.