Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene

Hsieh, Tsai‐Yuan; Shiu, Tzu-Yue; Chu, Nain-Feng; Chao, Tsu Yi; Chu, Heng-Cheng; Chang, Wei‐Kuo; Chao, You‐Chen; Huang, Haiyan

doi:10.4238/2014.january.28.12

Cited by 11 publications

(9 citation statements)

References 28 publications

(37 reference statements)

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“…[ 4 ] It is the most common inherited disorder of bilirubin metabolism, affecting 3% to 12% of the general population [ 5 ] (5%–10% of Caucasians [ 6 ] ), and is primarily characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis, which becomes clinically apparent during fasting, physical exercise, stress, or menstruation. [ 7 ]…”

Section: Introductionmentioning

confidence: 99%

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II

Sun

Zhang

et al. 2017

Medicine

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Diagnosis of Crigler-Najjar syndrome type II (CNS-II) and Gilbert syndrome (GS) based on the serum bilirubin concentration is difficult, because this parameter can fluctuate under certain conditions. The aim of this study was to explore differences in UGT1A1 gene mutations, which cause both CNS and GS, and pathological changes between CNS-II and GS.Ninety-five Chinese patients with hereditary unconjugated hyperbilirubinemia were enrolled in this study. Peripheral blood samples obtained from patients were used to evaluate bilirubin levels and for UGT1A1 gene testing. Percutaneous needle biopsy of the liver and staining of tissue samples with hematoxylin and eosin, Masson trichrome, reticulin, and Perl Prussian blue were performed for 59 patients. The Ishak scoring system was used to assess inflammatory activity and the extent of fibrosis.One hundred ninety-two UGT1A1 mutations at 6 sites were detected in the 95 patients; the most common mutation in GS was c.-3279T>G in the phenobarbital response enhancing motif of the UGT1A1 promoter, whereas the most common mutation in CNS-II was p.G71R. The frequency of heterozygous p.G71R mutations in CNS-II was significantly higher than that in GS (P = .001); however, the frequency of homozygous c.-3279T>G mutations in CNS-II was markedly lower than that in GS (P = .032). Among all patients with multiple mutations, the frequency of p.Y486D was significantly higher in CNS-II than in GS (P = .007). The frequency of compound c.-3279T>G, A(TA)7TAA, and p.G71R mutations in CNS-II was significantly higher than that in GS (P = .001). Among the 59 patients who underwent percutaneous needle biopsy, 20 had iron deposition in the liver. The frequency of hepatic iron deposition in CNS-II was significantly higher than that in GS (P = .002).The linked polymorphic mutations, A(TA)7TAA and c.-3279T>G in UGT1A1, were most strongly associated with GS, whereas mutations in the coding region, especially p.G71R and p.Y486D, were more strongly associated with CNS-II. Iron deposition was more common in liver biopsies from patients with CNS-II than in those with GS.

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Section: Introductionmentioning

confidence: 99%

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II

Sun

Zhang

et al. 2017

Medicine

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“…Direct sequencing method is frequently used for the identification of nucleotide 211G>A mutation in the coding exon 1 of UGT1A1 gene . In addition to direct sequencing method, TaqMan MGB SNP genotyping assay and DNA melting curve analysis have also been used to detect 211G>A mutation . In this study, we have established a PCR‐based RFLP method used for the molecular diagnosis of a second common heterozygous mutation (211G>A) in the coding exon 1 of UGT1A1 gene by identifying BsmBI RFLP patterns.…”

Section: Discussionmentioning

confidence: 99%

“…PCR‐amplified products were analysed by direct sequencing method. Furthermore, melting curve analysis for the identification of TATA‐Box genotypes of UGT1A1 gene was performed according to the previous description .…”

Section: Methodsmentioning

confidence: 99%

“…Direct sequencing method and TaqMan MGB SNP genotyping assay have been used to identify nucleotide 211G>A mutation in the coding exon 1 of UGT1A1 gene . Recently, melting curve analysis for the detection of nucleotide 211G>A mutation has also been described . DNA restriction fragment length polymorphisms (RFLPs), a simple and effective molecular diagnosis method, is used for the diagnosis of genetic disease that can be detected by the presence of fragments of different lengths after digestion of DNA samples with specific restriction endonucleases .…”

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confidence: 99%

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Restriction fragment length polymorphism effectively identifies exon 1 mutation of UGT1A1 gene in patients with Gilbert's Syndrome

Shiu

Huang

Lin

et al. 2015

Liver International

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“…Fluorescent labeled probes, acrylamide-modified primers and the use of Luxscan-10K/A (CapitalBio Company, China) are expensive. Other method, such as direct sequencing method, TaqMan MGB SNP genotyping assay, DNA melting curve analysis, Restriction Fragment Length Polymorphism (RFLP) method have been used to detect mutations of UGT1A1 gene for Gilbert's Syndrome diagnosis [15][16][17]. In this study, we applied dot blot hybridization assay with molecular probes for the first time to detect the T-3279G, A(TA)6/7TAA and G211A mutation of UGT1A1 gene.…”

Section: Biomedical Research 2018; 29 (10): 2111-2115mentioning

confidence: 99%

Molecular probes for identification of UDP-glucuronosyltransferase 1 gene polymorphisms for Gilbert's syndrome diagnosis

Wu¹,

Zhou²,

Song³

et al. 2018

biomedicalresearch

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The T-3279G mutation in Phenobarbital Responsive Enhancer Modulein (PBREM), TA-insertion in the TATA box, creating the A(TA)7TAA motif instead of the A(TA)6TAA, and G211A mutation in coding exon 1, particularly in Asians, of human UGT1A1 (UDP-glucoronosyltransferase) gene are the three common polymorphisms of Gilbert's syndrome. This article employed dot blot hybridization to detect the T-3279G, A(TA)6/7TAA and G211A mutation of UGT1A1 gene in 15 patients. In the dot blot hybridization assay, PCR products were denatured and spotted on positively charged nylon membranes instead of acrylamide-modified slides. Then three pairs of probes were labeled by digoxigenin and hybridized with the spotted array. After hybridization, the signal was visualized using TMB color development solution and all possible polymorphisms of the T-3279G, A(TA)6/7TAA and G211A in 15 Chinese patients with hyperbilirubinemia were successfully identified. The results of 15 samples by dotblot hybridization were consistent with the sequencing results. The data showed that dot blot hybridization assay is a quick and low cost method to detect UGT1A1 gene polymorphisms and helpful to diagnosis of Gilbert's syndrome.

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Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene

Cited by 11 publications

References 28 publications

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II

Restriction fragment length polymorphism effectively identifies exon 1 mutation of UGT1A1 gene in patients with Gilbert's Syndrome

Molecular probes for identification of UDP-glucuronosyltransferase 1 gene polymorphisms for Gilbert's syndrome diagnosis

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