[Analysis of familial intrahepatic cholestasis caused by ubiquitin-specific peptidase 53 gene mutation].
Source: PubMed, NCBI / U.S. National Library of Medicine
To investigate the clinical characteristics and gene mutation status of progressive familial intrahepatic cholestasis caused by a ubiquitin-specific peptidase 53 (USP53) gene mutation (USP53-FIC) in a family.A female infant patient with USP53-FIC and her family who presented to the Department of Gastroenterology, Children's Hospital Affiliated with Zhengzhou University, in May 2025 with a one-month history of jaundice and yellow urine, which worsened over a one-week period of ecchymosis, were selected as the study subjects. Peripheral blood samples were collected from the patient, her parents, and her elder brother for whole-exome sequencing of the family, followed by Sanger sequencing for validation.The patient was a 5-month-23-day-old female presenting primarily with jaundice of the skin and sclera, dark urine, and skin ecchymosis. Liver function tests indicated cholestasis, normal gamma-glutamyl transferase, and abnormal coagulation function. Whole-exome sequencing of the family revealed a compound heterozygous variant of c.1558C>T and c.829dup in the USP53 gene, inherited from her mother and father, respectively. Sanger sequencing confirmed that the patient's older brother carried the same variants. The c.1558C>T was previously reported as a pathogenic variant, while c.829dup was previously unreported. PVS1 + PM2_Supporting + PM3 was reported as a pathogenic variant according to the American Society for Medical Genetics and Genomics variant rating guidelines.The compound
Abstract
To investigate the clinical characteristics and gene mutation status of progressive familial intrahepatic cholestasis caused by a ubiquitin-specific peptidase 53 (USP53) gene mutation (USP53-FIC) in a family.A female infant patient with USP53-FIC and her family who presented to the Department of Gastroenterology, Children's Hospital Affiliated with Zhengzhou University, in May 2025 with a one-month history of jaundice and yellow urine, which worsened over a one-week period of ecchymosis, were selected as the study subjects. Peripheral blood samples were collected from the patient, her parents, and her elder brother for whole-exome sequencing of the family, followed by Sanger sequencing for validation.The patient was a 5-month-23-day-old female presenting primarily with jaundice of the skin and sclera, dark urine, and skin ecchymosis. Liver function tests indicated cholestasis, normal gamma-glutamyl transferase, and abnormal coagulation function. Whole-exome sequencing of the family revealed a compound heterozygous variant of c.1558C>T and c.829dup in the USP53 gene, inherited from her mother and father, respectively. Sanger sequencing confirmed that the patient's older brother carried the same variants. The c.1558C>T was previously reported as a pathogenic variant, while c.829dup was previously unreported. PVS1 + PM2_Supporting + PM3 was reported as a pathogenic variant according to the American Society for Medical Genetics and Genomics variant rating guidelines.The compound heterozygous variant c.1558C>T and c.829dup in the USP53 gene are the genetic cause of this USP53-FIC in a family. USP53-FIC should be suspected for infants who suddenly develop cholestasis accompanied by coagulation disorders but normal gamma-glutamyl transferase levels. Genetic testing is helpful in clarifying the diagnosis and guiding treatment. The c.829dup variant enriches the variant spectrum of the USP53 gene.