OBJECTIVE: To explore the genetic etiology and differential diagnosis for a patient with jaundice. METHODS: Clinical data of the patient and his parents were collected. Genes associated with metabolic liver diseases were subjected to high-throughput sequencing. The pathogenicity of the candidate variants was predicted by using bioinformatics software. RESULTS: High-throughput sequencing revealed that the proband has harbored two variants of the ABCC2 gene (NM_000392) including c.3011C>T (p.T1004I) and c.3541C>T (p.R1181X), which were respectively inherited from his father and mother. Both variants have been previously unreported and predicted to be pathogenic by bioinformatics analysis. CONCLUSION The proband was diagnosed with Dubin-Johnson syndrome due to the compound heterozygous variants of the ABCC2 gene. Genetic testing has enabled accurate differential diagnosis of Dubin-Johnson syndrome in this patient.
Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Jaundice, Chronic Idiopathic/pathology* ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Mutation

OBJECTIVE: To explore the genetic etiology in four patients with hyperbilirubinemia, and discuss the correlation between clinical characteristics and molecular basis. METHODS: The data of clinical manifestation and auxiliary examinations were collected. Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases. Suspected variants were verified by Sanger sequencing. RESULTS: All of the four patients were males with normal liver enzymes. It was revealed that all the patients had heterozygous variants, among which c.3011C>T, c.2443C>T and c.2556del were the variants which have not been reported previously. CONCLUSION All of the patients were diagnosed as Dubin-Johnson syndrome (DJS) caused by ABCC2 gene variants. The novel variants add to the spectrum of genetic variants of the disease. Because of the favorite prognosis, precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments. At the same time, it could provide pertinent genetic counseling for the families.
DNA ; Female ; Heterozygote ; Humans ; Jaundice, Chronic Idiopathic/genetics* ; Male ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Phenotype

A family was studied in which three members in the sibship belonging to the fourth generation were found to have Rotor’s syndrome. More detailed examinations including blood studies, liver profiles, oral cholecystograms, and liver biopsies where performed on the affected siblings. The results were related to what is at present known about the features and mechanisms of Rotor’s syndrome, pari passu the current concept of bilirubin metabolism. It is suggested that the constant finding, and possibly the only characteristic one in Rotor’s syndrome, is the absence of abnormal hepatic cell pigmentation. Pedigree analysis of the present family shows that the transmission of this disorder may be conditioned by an autosomal recessive gene.
Hyperbilirubinemia, Hereditary

OBJECTIVE: To explore the genetic basis for a patient featuring Rotor syndrome. METHODS: Clinical data of the patient was collected. Whole exome sequencing (WES) based on high-throughput sequencing technology was carried out. Long-interspersed element-1 (LINE-1) insertion in intron 5 of the SLCO1B3 gene was detected by using tri-primer single tube PCR. RESULTS: WES revealed that the patient has carried homozygous c.1738C>T nonsense variants of the SLCO1B1 gene. He was also found to harbor a homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene, which has caused skipping of exon 5 or exons 5 to 7 and introduced a stop codon in the SLCO1B3 transcript. CONCLUSION The homozygous c.1738C>T variant of the SLCO1B1 gene and homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene probably underlay the Rotor syndrome in this patient.
Exons/genetics* ; Homozygote ; Humans ; Hyperbilirubinemia, Hereditary ; Introns/genetics* ; Liver-Specific Organic Anion Transporter 1 ; Male ; Whole Exome Sequencing

A case of Gilbert syndrome (GS) with a heterozygous mutation in the gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. *28 and c.211G>A heterozygous mutations in gene were found, which may be another type of mutation causing GS in Chinese population.
Asian Continental Ancestry Group ; Bilirubin ; Gilbert Disease ; genetics ; Glucuronosyltransferase ; genetics ; Heterozygote ; Humans ; Mutation

OBJECTIVE: To explore the clinical characteristics and molecular basis for a Chinese boy affected with jaundiced skin and liver disease. METHODS: The patient was subjected to clinical examination and laboratory tests. Genomic DNA of the patient and his parents was extracted and analyzed by using next generation sequencing (NGS). Suspected mutations were analyzed with bioinformatic software and verified by Sanger sequencing. RESULTS: The patient had jaundice in his eyes and skin. Serum bilirubin was elevated along with hepatomegaly. Next generation sequencing showed that the patient has carried c.18C>A(p.C6X) and c.2556delA mutations in the MRP2 gene, which were respectively inherited from his father and mother. CONCLUSION The missense mutation c.18C>A and frameshift mutation c.2556delA probably account for the disease. NGS has provided a powerful tool for the diagnosis of rare genetic diseases including Dubin-Johnson syndrome.
Asian Continental Ancestry Group ; DNA ; High-Throughput Nucleotide Sequencing ; Humans ; Jaundice, Chronic Idiopathic ; Male ; Mutation

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9.5-month-old male infant was referred to the hospital due to abnormal liver function discovered over 9 months. The major clinical presentation was prolonged jaundice since neonatal period. A series of biochemistry analysis revealed markedly elevated total bilirubin, conjugated bilirubin and total bile acids. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. Physical examination revealed jaundiced skin and sclera, and a palpable liver 3 cm below the right subcostal margin with medium texture. The spleen was not enlarged. Genetic analysis revealed a splice-site variant c.3988-2A>T and a nonsense variant c.3825C>G (p.Y1275X) in the ABCC2 gene of the infant, which were inherited from his mother and father respectively. The former had not been previously reported. Then ursodeoxycholic acid and phenobarbital were given orally. Half a month later, as a result, his jaundice disappeared and the biochemistry indices improved. However, the long-term outcome needs to be observed. Literature review revealed that neonates/infants with DJS presented with cholestatic jaundice soon after birth as the major clinical feature, and the ABCC2 variants exhibited marked heterogeneity.
Bile Acids and Salts ; Bilirubin ; Humans ; Infant ; Jaundice ; Jaundice, Chronic Idiopathic ; genetics ; Male ; Multidrug Resistance-Associated Proteins ; genetics ; Ursodeoxycholic Acid

BACKGROUND: Hyperbilirubinemia is a common postoperative complication. Elevated direct bilirubin (D-Bil) and indirect bilirubin (I-Bil) levels are related to different pathophysiologies; therefore, their associations with outcomes also differ. However, there have been few comparative studies of such associations in postoperative patients. METHODS: This retrospective study compared the associations of postoperative D-Bil and I-Bil with outcomes. We included adult patients requiring postoperative intensive care for more than 48 hours between 2008 and 2013, except those undergoing liver operations. The number of patients was determined using a power calculation. D-Bil and I-Bil measurements were obtained on postoperative days (POD) 1 and 2. The primary outcome was defined as hospital mortality, with the number of ICU-free survival days (IFSD) at POD 28 as the secondary outcome. RESULTS: The study population consisted of 1,903 patients with a mortality rate of 2.2%. D-Bil at POD 1 was significantly higher in non-survivors than survivors (P = 0.001), but I-Bil at POD 1 showed no such relation (P = 0.209). Multivariate logistic analysis indicated that higher postoperative D-Bil was independently associated with increased postoperative mortality (POD 1: adjusted odds ratio [OR] = 2.32, P < 0.001; POD 2: adjusted OR = 1.95, P < 0.001), but I-Bil showed no such relation (POD 1: P = 0.913; POD 2: P = 0.209). Increased D-Bil was independently associated with decreased IFSD at POD 28 (POD 1: adjusted coefficient = −1.54, P < 0.001; POD 2: −1.84, P < 0.001). In contrast, increased I-Bil at POD 1 was independently associated with increased IFSD at POD 28 (POD 1: adjusted coefficient = +0.39, P = 0.021; POD 2: +0.33, P = 0.080). CONCLUSIONS: D-Bil indices have a higher capability than I-Bil for predicting poorer outcomes in critically ill postoperative patients.
Adult ; Bilirubin ; Critical Care ; Critical Illness ; Gilbert Disease ; Hospital Mortality ; Humans ; Liver ; Mortality ; Odds Ratio ; Postoperative Complications ; Retrospective Studies ; Survivors

A two-year-old girl was admitted due to repeated yellowing of the skin and sclera for 2 years and had no other specific symptoms or signs. The use of phenobarbital could relieve the symptoms of jaundice. Multiple examinations showed increased indirect bilirubin levels, and the results of aminotransferases and liver imaging were normal. There was no evidence of hemolysis. The analysis of UGT1A1 gene in her family found that this child had double homozygous mutation of c.211G>A(G71R) and c.1456T>G(Y486D), which had been reported as the pathogenic mutation for Gilbert syndrome. Her parents carried double heterozygous mutation of G71R and Y486D and had no symptom of jaundice. The child was diagnosed as having Gilbert syndrome. It is concluded that as for patients with unconjugated hyperbilirubinemia which cannot be explained by liver damage and hemolysis, their family history should be investigated in detail and gene analysis should be performed as early as possible, in order to identify congenital bilirubin metabolic disorders.
Child, Preschool ; Female ; Gilbert Disease ; diagnosis ; Glucuronosyltransferase ; genetics ; Humans ; Mutation ; Sclera ; pathology ; Skin ; pathology

OBJECTIVETo detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type II.

METHODSBlood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction (PCR) and direct sequencing. The child was followed up until the age of 3 years and 6 months.

RESULTSThe patient showed persistent unconjugated hyperbilirubinemia. Sequencing of the UGT1A1 gene has detected a rare heterozygous c.610 A>G (p.Met204Val) mutation in the exon 1, in addition with a heterozygous c.1091 C>T (p.Pro364Leu) mutation in exon 4. The two mutations were inherited from his father and mother, respectively. The patient was diagnosed with Crigler-Najjar syndrome type II and received oral phenobarbital treatment.

CONCLUSIONThe compound UGT1A1 gene mutation probably accounts for the disease in the patient manifesting persistent mild unconjugated hyperbilirubinemia. Genetic counseling and prenatal diagnosis should be provided for his family.