Crigler-Najjar syndrome type 2 complicating cholecystitis in a patient with UGT1A1 gene double homozygous mutations.
10.1007/s11684-025-1142-6
- Author:
Jianhui ZHANG
1
;
Rongrong CHEN
1
;
Xiang CHEN
2
;
Ying CHEN
1
;
Qilin CHEN
1
;
Shiyun LU
3
,
4
;
Jiewei LUO
5
;
Xiaoling ZHENG
6
;
Mengshi CHEN
7
Author Information
1. Department of Traditional Chinese Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China.
2. The First Clinical Medical College, Nanchang University, Nanchang, 330006, China.
3. Department of Traditional Chinese Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China. lushiyun121739@
4. com.
5. Department of Traditional Chinese Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China. docluo0421@aliyun.com.
6. Department of Traditional Chinese Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China. xiaolingzheng@fjmu.edu.cn.
7. Department of Traditional Chinese Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China. 9201551241@fjmu.edu.cn.
- Publication Type:Case Reports
- Keywords:
UGT1A1 gene;
Crigler-Najjar syndrome;
Gilbert syndrome;
double homozygous mutations
- MeSH:
Humans;
Male;
Glucuronosyltransferase/genetics*;
Adult;
Crigler-Najjar Syndrome/complications*;
Cholecystitis/etiology*;
Homozygote;
Mutation;
Pedigree
- From:
Frontiers of Medicine
2025;19(4):675-680
- CountryChina
- Language:English
-
Abstract:
Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)7TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)7TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)7TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
