Mutations In UGT1A1 Gene Research Articles

Visceral crisis in a patient with pancreatic ductal adenocarcinoma with DPYD and UGT1A1 gene mutations: case report, literature review, and viewpoint

Visceral crisis in a patient with pancreatic ductal adenocarcinoma with DPYD and UGT1A1 gene mutations: case report, literature review, and viewpoint

Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

Coexistence of mutations of Gilbert’s syndrome and Crigler-Najjar syndrome in an infant with unconjugated hyperbilirubinemia—a case report

BackgroundJaundice in the newborn period is a very common entity; rare inherited causes are often forgotten. Persistent unconjugated hyperbilirubinemia in the intermediate levels with non-hemolytic features must prompt the necessity for evaluating for genetic defects in bilirubin metabolism.Case presentationThree-and-a-half-month-old first-born girl of consanguineous marriage presented with jaundice from day 5 of life. Dark yellow color urine or pale stools were not present. Antenatal and birth history was normal. She had mild pallor and icterus and no hepatosplenomegaly. Total serum bilirubin was 8.2 mg/dl, and direct was 0.4 mg/dl. Workup for hemolytic anemia, thyroid function test, and sonography of abdomen was normal. Syrup phenobarbitone was started, and bilirubin levels after dropped to 2 mg/dl. Crigler-Najjar type II syndrome (CN II) or Gilbert’s syndrome (GS) was suspected. Next-generation sequencing for UGT1A1 gene mutation showed homozygous missense mutation consistent with CN II and 7 TA repeats in the promoter region consistent with GS. Bilirubin levels gradually fell after starting oral phenobarbitone syrup, and at 5 years of age, a trial of withholding phenobarbitone was given, and bilirubin levels remained lower, and she is asked to follow-up with bilirubin levels every 15 days to assess the need for reintroducing the therapy. Parents are planning for a second pregnancy, and a preconception genetic counseling has been done.ConclusionGenetic confirmation of coexistence of mutations causing GS and CN II have an implication on long-term neurological complications of unconjugated hyperbilirubinemia in stress or crisis situations. Prenatal diagnostic testing must be advised for detecting homozygous UGT1A1 mutations to diagnose CN II and Gilbert mutations for each of the future pregnancies. Considering the side effects of long-term phenobarbitone therapy, the decision can be taken on case-to-case basis of stopping the therapy while monitoring TSB levels.

UGT1A1 variants in Chinese Uighur and Han newborns and its correlation with neonatal hyperbilirubinemia.

To explore the correlation between UGT1A1 variant and neonatal hyperbilirubinemia in Chinese Uighur and Han populations. We conducted this study in Urumqi, China. Umbilical cord blood specimens and clinical information of term infants born in the studied center were collected. Variation status of UGT1A1 was determined by direct sequencing or capillary electrophoresis analysis. 102 Uighur and 99 Han normal term neonates, together with 19 hospitalized term newborns (10 Uighur and 9 Han) due to significant hyperbilirubinemia were enrolled into the final analysis. The incidence of neonates with high-risk transcutaneous bilirubin level (TCB) were much higher in Han newborns than in Uighur newborns(P = 0.01). Also, there was statistically significant difference in (TA) 7 promoter mutation of UGT1A1 between Han and Uighur group(χ2 = 4.675, P = 0.03). Furthermore, exon mutation (c.211 and /or c.1091) in UGT1A1 gene was significantly associated with increased TCB level (ORadj = 1.41, 95%CI: 0.25-2.51, P = 0.002) and higher risk of hyperbilirubinemia in both Han and Uighur infants after adjusted for covariates (ORadj = 2.21, 95%CI: 1.09-4.49, P = 0.03). In conclusion, UGT1A1 promoter polymorphism seem to be an important genetic modulator of plasma bilirubin level and neonatal hyperbilirubinemia risk within ethnic groups. Genetic assessment of UGT1A1 coding variants may be useful for clinical diagnosis of neonatal jaundice.

UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi

To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.

Study single nucleotide polymorphism in Promoter region of UGT1A1 Gene in Iraqi Patients with Gilbert's syndrome

This study aimed to detect genetic variants of the UGT1A1 gene in patients with Gilbert's syndrome. To detect this, primers were designed; PCR and direct sequencing were done for the promoter area of the gene as a diagnostic tool for the detection of any polymorphism. Variation and polymorphism were detected within the promoter mutants of the UDP glycosyltransferase _UGT1A1 gene that causes hyperbilirubinemia in a group of Iraqi patients compared with a group of the normal healthy individual as controls. The patients with hyperbilirubinemia in this study were 30 in which the total bilirubin level was more than 12 mg/dl serum; they included 25 males and 5 females, while the control group consisted of 20 healthy individuals. This study was carried out from September 2019 till April 2021. The result displayed high occurrence of Gilbert syndrome within male patients than in females, and regarding the analyses of mutation of bilirubin UDP glycosyltransferase _UGT1A1 gene, it is clear that the genotypic distribution of variation among the hyperbilirubinemia patients included all 30 patients, while SNP was detected in 18 patients out of 30 which indicate that the UGT1A1 gene mutation was a likely risk factor for the development of hyperbilirubinemia related Gilbert syndrome in Iraq. The homozygous and heterozygous polymorphisms A/G inside the promoter region of the UGT1A1 gene were effectively identified by sequencing. Our finding suggests that TA repeats and allele of UGT1A1 polymorphism A/G are associated with Gilbert's syndrome and act as genetic markers of this disease in Iraqi patients. To analyze data and sequence variation in gene, generous software was used after amplifying the gene. All processes include DNA extraction, PCR amplification, sequencing, and assembly.

UGT1A1-related Bilirubin Encephalopathy/Kernicterus in Adults.

Background and AimsBilirubin encephalopathy/kernicterus is very rare in adults. This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus.MethodsSanger sequencing analysis was performed to identify UGT1A1 gene mutations in the patients and their families. Bioinformatics analysis was used to predict the potential functional effects of novel missense mutations. Clinical manifestations and biochemical parameters were collected and analyzed.ResultsTwo patients with Crigler-Najjar syndrome type II (CNS2) developed kernicterus in adulthood. Sanger sequencing identified a compound heterozygous mutation in the UGT1A1 gene in patient 1, which was inherited from his mother (G71R) and his father (c.-3279T>G; S191F). Patient 2 carried three heterozygous mutations, namely G71R, R209W and M391K; among which, the M391K mutation has not been reported before. Multiple prediction software showed that the M391K mutation was pathogenic. Symptoms were relieved in the two patients after phenobarbital and artificial liver support treatment. Patient 1 also underwent liver transplantation.ConclusionsAdults with CNS2 are at risk for kernicterus. Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus.

Study of UGT1A1 Gene Mutation in People Suspected of Hyperbilirubinemia and Its Relationship with Fatty Liver Syndrome by Tetra ARMS-PCR Technique

Hyperbilirubinemia is one of the most common disorders in the world. The disease has spread out the Middle East to Africa. The importance of this disease is high due to its widespread prevalence in the world. In this study, to investigate hyperbilirubinemia and the difference between the mutations in the UGTA1 gene with hyperbilirubinemia and the fatty liver syndrome was selected from the SNPs involved in expressing the UGTA1 gene named rs372326047.DNA genomic was extracted and one pair of primer for amplifying of the rs372326047 was designed with the help of the Oligo Version 7.0. After the PCR reaction, samples were sequenced to determine of the fragment of UGTA1 gene. Figures 1 and 2 showed the sequences were analyzed using the Blast program. Results observed that no mutation between UGTA1 gene. In Table 1. Ten cases from forty samples were selected including, healthy, carrier, sick and different parameters that were questioned from them. Patients have been heart diseases, diabetic-hepatic, and some patients did not have a history of inheritance diseases in family, rate of Hb in some cases was high (more than ten). Most of the cases also had high anemia and regarding some cases, the history of hyperbilirubinemia and its relationship with fatty liver diseases in family was positive and some cases was negative. Table 2. One-way ANOVA followed by Tuckey's post hoc test and HWE frequency of allelic and genotyping of nucleotide of TT, TC and CC of rs372326047of UGTA1 gene in cases and normal population respectively. Therefore, the results of this study show that there is no relationship between mutations in the rs372326047 of UGTA1 gene in hyperbilirubinemia and its relationship with fatty liver syndrome.

Advances in studies on the polymorphism of UGT1A1 gene in neonates with unexplained hyperbilirubinemia

Neonatal hyperbilirubinemia is a common clinical symptom in the neonatal period. Severe jaundice can cause neonatal bilirubin encephalopathy. Clinically because severe hyperbilirubinemia more causes, the cause of hemolysis and infection is more common, this also accounted for a certain proportion of unknown reasons. UGT1A1 is a key enzyme for bilirubin metabolism, and unexplained jaundice is associated with a decrease in UGT1A1 activity caused by mutations in UGT1A1 gene, leading to neonatal persistent jaundice. The relationship between neonatal unexplained hyperbilirubinemia and UGT1A1 gene polymorphism was reviewed.

Population genetic research of the mutation in ugt1a1 gene associated with reduced activity of liver UDP-glucuronosyltransferase A1

Aim. To explore allele and genotype frequencies of the rs8175347 polymorphism within the UGT1A1 gene in Kemerovo Region. Materials and Methods. The study sample included 64 male and 68 female inhabitants of the Kemerovo Region. Upon DNA isolation from the peripheral blood leukocytes, we conducted allele-specific polymerase chain reaction followed by electrophoretic detection of the genotype. Results. The frequency of minor allele *28 of rs8175347 polymorphism, which is associated with the downregulation of UDP-glucuronosyltransferase А1 in the liver, was 33.3%, while the frequency of *28/*28 genotype was 13.6% and did not significantly differ in the examined men and women. Conclusion. High frequency of the *28/*28 genotype in the studied sample suggests a high prevalence of reduced UDP-glucuronosyltransferase А1 activity and associated conditions including Gilbert’s syndrome and adverse drug reactions.

Analysis of mutation site characteristics of Gilbert syndrome and Crigler--Najjar syndrome in relation to uridine diphosphate glucuronosyltransferase A1 gene

Objective: To investigate the mutation characteristics and clinical relevance of Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1) gene. Methods: The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases. Results: A total of 163 mutation sites were found in the UGT1A1 gene since November 16, 2018. The following patterns existed at the above sites: (1) the numbers of gene mutations occurring between different exons of UGT1A1 was related to GS or CNS phenotypes, and were positively correlated with the length of the exon; (2) nonsense point mutations was mainly occurred in type I of CNS; (3) GS, Crigler-Najjar syndrome type II compound heterozygous mutation sites had a certain combination and distribution, among which - 3279t > G mutation was found in all four GS complex heterozygous compositions; (4) UGT1A1 gene mutation sites reported in Asia had marked aggregation in c.211-c.558. Conclusion: UGT1A1 gene mutation characteristics and clinical relevance varies with different mutation sites, reporting areas and populations. This study has reference value for basic research and clinical diagnosis and treatment of GS and CNS.

Patient with Gilbert Syndrome A Case Report and Review of the Literature

One of the Gilbert syndrome genetic diseases that is characterized by the presence of a genetic mutation in UGT1A1 gene, which is responsible for uridine diphosphate glucuronosyl transferase enzyme, responsible for the binding of bile, and thus the ease of its release from the liver and its non-accumulation in the body. A middle-aged man suffers from jaundice, although all clinical, laboratory, and imaging tests are normal. Hemolysis was excluded by the fact that the blood image did not include the presence of foreign cells, as well as reticulocyte count, and hemoglobin concentration in their normal rates, so it was excluded that the main cause of high bilirubin was the occurrence of hemolysis. So he was diagnosed with Gilbert's syndrome.

The relationship between hyperbilirubinemia and the promoter region and first exon of UGT1A1 gene polymorphisms in Vietnamese newborns.

To investigate the relationship between unexplained indirect hyperbilirubinemia of Vietnamese newborns and the polymorphism of the promoter TATA box and exon 1 of bilirubin uridine diphosphate glucuronosyltransferase (UGT1A1) gene. A total of 149 neonates were divided into the hyperbilirubinemia group (n = 99) and control group (n = 50). The gene polymorphisms of UGT1A1 gene in the two groups were detected by PCR and direct sequencing, which revealed the relationship between UGT1A1 polymorphism with neonatal hyperbilirubinemia of neonates. The types of UGT1A1 polymorphism in the hyperbilirubinemia group and the peak total serum bilirubin (PSB) levels with different genotypes were observed. (1) (TA)7 insertion mutation, 211G>A, 189C>T, 190G>A, 378C>T and 686C>A were detected. (2) The allele frequency of 211G>A allele mutation was significantly different between the two groups (p < 0.05). (3) Logistic regression analysis showed that homozygosity and heterozygosity of 211G>A were both significantly associated with neonatal hyperbilirubinemia. (4) In the hyperbilirubinemia group, the peak total serum bilirubin level of 211G>A homozygous neonates was higher than that of the wild-type neonates (p < 0.05). We noted that there was an association between neonates with unexplained indirect hyperbilirubinemia in Vietnam and the polymorphism of UGT1A1c.211G>A. In addition, the homozygous 211G>A polymorphism was related to the degree of hyperbilirubinemia. Our article provided data on UGT1A1 polymorphism distribution in the Vietnamese population, which have not been reported yet. Our findings revealed that mutations in UGT1A1 gene are risk factors for unexplained hyperbilirubinemia in Vietnamese neonates. Our article will strengthen the cognition of neonatal jaundice at the genetic level in the pediatric field in Vietnam.

2438 An Unusual Cause of Jaundice: A Rare Diagnosis of Crigler-Najjar Type 2

INTRODUCTION: Crigler Najjar is an uncommon genetic disorder that results in elevated unconjugated bilirubin due to its impaired conjugation and excretion within the liver. Here we report a case of this unusual disorder in a relatively asymptomatic patient. CASE DESCRIPTION/METHODS: A 21-year-old woman with no significant past medical history presented with 1 year of intermittent jaundice, 20 pound unintentional weight loss, and decreased appetite. The patient reported recent travel to Cuba, but denied any known sick contacts. She also denied any pruritis, abdominal pain, nausea, or diarrhea. Her family history was notable for pancreatic adenocarcinoma. Social history was unremarkable. On physical exam, the patient was ill appearing with moderate scleral icterus and jaundice. Lab work demonstrated isolated unconjugated hyperbilirubinemia (Total Bilirubin: 7.5, conjugated: 0.4, unconjugated: 7.1). Right upper quadrant ultrasound and CT abdomen and pelvis were unrevealing as to the etiology of the patient's hyerbilirubinemia. Extensive testing for a variety of infectious, hereditary, hematological, and rheumatologic disorders were all negative as well. Further advanced genetic testing revealed a heterozygous UGT1A1 gene mutation, ultimately diagnosing the patient with Crigler-Najjar type 2 (CN2). Her symptoms resolved spontaneously without any intervention. DISCUSSION: CN2 is due to a partial deficiency of the enzyme uridine diphosphate-glucuronyl transferase (UGT1A1). Unlike the homozygous form of the disease where there is a total deficiency of the enzyme, usually resulting in death at an early age, the heterozygous form (type 2) is typically more benign in its course. While patients are relatively asymptomatic, they can develop hyperbilirubinemia in stressful situations, after surgery, or with certain medications. It is important to consider CN2 in patients with intermittent unconjugated hyperbilirubinemia. This is especially true in young women, such as this patient, as it can affect neonates during pregnancy. Unfortunately, due to the low prevalence of this, it is often a diagnostic challenge for clinicians.

UGT1A1 gene mutation as a marker indicating there is a high risk of Gilbert's syndrome: Theoretical and applied aspects

UGT1A1 gene mutation as a marker indicating there is a high risk of Gilbert's syndrome: Theoretical and applied aspects

Мутация гена UGT1A1 как маркер высокого риска возникновения синдрома Жильбера: научно-прикладные аспекты

Мутация гена UGT1A1 как маркер высокого риска возникновения синдрома Жильбера: научно-прикладные аспекты

A novel UGT1A1 gene mutation causing severe unconjugated hyperbilirubinemia: a case report

BackgroundCrigler-Najjar syndrome (CNs) presents as unconjugated hyperbilirubinemia, as a result of UGT1A1 deficiency, and can be categorized in a severe (type I) and mild (type II) phenotype. CNs type II patients usually benefit from phenobarbital treatment that induces residual UGT1A1 activity.Case presentationHere we present a CNs type II patient that is not responsive to phenobarbital treatment, which can be explained by two heterozygous mutations in the UGT1A1 gene. A 3 nucleotide insertion in the HNF-1α binding site in the proximal promoter previously reported in a Crigler-Najjar patient on one allele and a novel two nucleotide deletion in exon 1, resulting in a frameshift and a premature stop codon.ConclusionIn newly diagnosed CNs patients with unconjugated bilirubin levels consistent with CNs type II but that are unresponsive to phenobarbital treatment, disruption of the HNF-1α binding site in the proximal promoter should be considered as a probable cause. Upon confirming a mutation in the HNF-1α site, phenobarbital treatment should be stopped or at least be reconsidered because of its sedative effects and its teratogenic properties.

Study of Gilbert's Syndrome-Associated UGT1A1 Polymorphism in Jaundiced Neonates of ABO Incompatibility Hemolysis Disease.

This study aimed to assess the probable relationship between icter in neonates with ABO incompatibility hemolysis and UGT1A1 gene polymorphism. There were 65 ABO hemolytic disease of the newborn (HDN) neonates of full term in the study group and 82 non-ABO HDN neonates of full term in the compared group. We tested the UGT1A1 gene mutation of neonates of ABO HDN and non-ABO HDN. We compared the incidence of hyperbilirubinemia between neonates with and without UGT1A1 mutations in the ABO HDN and non-ABO HDN, to determine the relationship between icter in neonates with ABO HDN and UGT1A1 gene polymorphism. SPSS 13.0 were used to analyze those two groups' data. There was statistically significant difference of the serum bilirubin level between the Gly71Arg homozygous and no mutation group in the ABO HDN patients (p < 0.05). When hyperbilirubinemia was defined as serum bilirubin concentration >342 μmol/L, the incidence of hyperbilirubinemia between patients of UGT1A1 and non-UGT1A1 mutations in the ABO HDN group was significantly different (p < 0.05). But in the non-ABO HDN group, no significant difference was found. Individuals with Gly71Arg homozygous contributed to their hyperbilirubinemia in ABO HDN patients.

Analysis of the low functional allele 7(TA) of the UGT1A1 gene in healthy population in the Western region of Ukraine

Gilbert's syndrome, GS (non-hemolytic anemia) is a pathological condition caused by enzyme (uridine diphosphate glucuronosyltransferase) failure to degrade bilirubin because of UGT1A1 gene mutations, which generally are TA insertions in the promoter region. Disorder entails constantly high level of bilirubin in the blood, and its toxicity causes symptoms manifestation. The pathology doesn’t require therapy, but it increases the risk of concomitant disorders and requires a special approach when prescribing therapy with drugs. The frequency of Gilbert's syndrome ranges from 0.6% to 43% worldwide, the frequency in Ukraine is not known exactly. Thus, the aim of the work was, based on analysis of published data, to study the world distribution of Gilbert's syndrome risk alleles, to find their associations with other pathological conditions, and to establish the frequency of the low-functional allele and various genotypes in TA [A(TA)6TAA] locus of UGT1A1 gene among residents of the Western region of Ukraine. Blood samples from 130 healthy residents of the Western region of Ukraine were collected, DNA samples were isolated by salting method. DNA amplification was performed by PCR followed by 10% PAG analysis and HRM analysis (high resolution melting). The pathogenic allele frequency was 34.3%, the frequency of the ancestral allele was 65.7%. The frequency of the mutant homozygous genotype was 14.6%, which coincides with published data. The frequency of the mutant genotype equals 8–18% for European countries, so our data coincide with results of population studies of European countries residents. It should be noted that these 14.6% of population are of high risk of concomitant disorders, such as colorectal cancer in men, breast cancer in women, diseases of the gastrointestinal tract, biliary calculus and formation of kidney stones. Thus, it is advisable to analyze 7(TA) alleles (risk alleles for Gilbert's syndrome) of the UGT1A1 gene in patients with hyperbilirubinemia of undetermined origin to diagnose Gilbert's syndrome.

Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia

Objective: To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. Methods: A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ (2) test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test. Results: Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert's syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) μmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) μmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05). Conclusion: The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.