Genetic and biochemical study of dual hereditary jaundice: Dubin–Johnson and Gilbert’s syndromes. Haplotyping and founder effect of deletion in ABCC2

Šlachtová, Lenka; Šeda, Ondřej; Behunova, Jana; Mistrík, Martin; Martásek, Pavel

doi:10.1038/ejhg.2015.181

Cited by 11 publications

(9 citation statements)

References 36 publications

(35 reference statements)

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“…In our patient, due to the absence of cholestasis as suggested by unchanged or slightly modified serum concentrations of enzymatic markers of cholestasis (ALP and GGT) and confirmed by MRCP, we speculated for the first time that the severe and prolonged mixed hyperbilirubinemia may derive from a genetic predisposition causing a metabolic deficit. A dual hereditary jaundice, due to a compound defect of bilirubin conjugation (Gilbert syndrome/UGT1A1) and transport (Dubin-Johnson syndrome/ABCC2) was previously described [10]; however, our case presented two other additional hereditary defects in the SLCO1B1 and ABCG2 genes.…”

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confidence: 55%

An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?

Falvella

Angeli

Cordier

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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Acute hepatitis A virus (AHAV) infection is a self-limited condition that usually spontaneously recovers in 2-8 weeks. While in children under 6 years of age AHAV is often asymptomatic, >70% of adults manifest symptoms together with typical laboratory findings [1]. AHAV is serologically diagnosed by the detection of anti-HAV IgM, which persists 2-6 months after infection. Laboratory results during AHAV show a marked increase (usually 10 to 40 times the upper reference limit [URL]) in serum alanine aminotransferase (ALT) activity, together with high total bilirubin (TB) (average peak of 171.0 μmol/L, mainly consisting of the conjugated form) and moderately (<3 URL) increased alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) [2]. With resolution of AHAV, conjugated bilirubin (CB) is rapidly cleared and its serum concentrations return to normal quickly. However, 10%-20% of patients develop prolonged cholestasis lasting for >6 months [1].Bilirubin, which is a major end-product of heme breakdown, is physiologically glucuronidated in the liver and then excreted into the bile. The mechanisms of bilirubin excretion, and of hyperbilirubinemia causes, are

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mentioning

confidence: 55%

An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?

Falvella

Angeli

Cordier

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…For example, for ICD10 code E80: disorders of porphyrin and bilirubin metabolism, we found multiple strong signals involving specific exons across several UDP-glucuronosyltransferase genes (UGT1A10, 9, 8, 7, 6 and 4) (Figure 3E). Genetic variation of UGT1A genes has been associated with disorders of bilirubin metabolism including Gilbert's syndrome by multiple previous SNP GWAS studies (120,121) with, for example, very strong association signal at UGT1A10 for the intron variant rs6742078 (2_233763993_G_T) (122). This specific SNP has also been linked to other lipid metabolism disorders such as Gallstones Disease (GSD) (123) and although studies looking at CNV burden analysis of lipid metabolism genes has shown a significant enrichment in GSD cases none of those associations could be attributed to any single gene (124).…”

Section: First Occurrences Icd10 Code Copy Number Variation Associationsmentioning

confidence: 99%

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

Fitzgerald

Birney

2021

Preprint

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Copy number variation (CNV) has long been known to influence human traits having a rich history of research into common and rare genetic disease and although CNV is accepted as an important class of genomic variation, progress on copy number (CN) phenotype associations from Next Generation Sequencing data (NGS) has been limited, in part, due to the relative difficulty in CNV detection and an enrichment for large numbers of false positives. To date most successful CN genome wide association studies (CN-GWAS) have focused on using predictive measures of dosage intolerance or gene burden tests to gain sufficient power for detecting CN effects. Here we present a novel method for large scale CN analysis from NGS data generating robust CN estimates and allowing CN-GWAS to be performed genome wide in discovery mode. We provide a detailed analysis in the large scale UK BioBank resource and a specifically designed software package for deriving CN estimates from NGS data that are robust enough to be used for CN-GWAS. We use these methods to perform genome wide CN-GWAS analysis across 78 human traits discovering 862 genetic associations that are likely to contribute strongly to trait distributions based solely on their CN or by acting in concert with other genetic variation. Finally, we undertake an analysis comparing CNV and SNP association signals across the same traits and samples, defining specific CNV association classes based on whether they could be detected using standard SNP-GWAS in the UK Biobank.

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“…Hitherto, more than 40 ABCC2 variants causing DJS, has been documented. 1,2 Intrahepatic cholestasis of pregnancy (ICP) occurs commonly during the late second or third trimester of pregnancy. Adverse pregnancy outcomes include spontaneous preterm labor, fetal distress, fetal asphyxia events, and third trimester intrauterine death.…”

Section: Novel Compound Heterozygous Abcc2 Variants In Patients With mentioning

confidence: 99%

Novel compound heterozygous ABCC2 variants in patients with Dubin‐Johnson syndrome and intrahepatic cholestasis of pregnancy

et al. 2018

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Genetic and biochemical study of dual hereditary jaundice: Dubin–Johnson and Gilbert’s syndromes. Haplotyping and founder effect of deletion in ABCC2

Cited by 11 publications

References 36 publications

An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?

An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

Novel compound heterozygous ABCC2 variants in patients with Dubin‐Johnson syndrome and intrahepatic cholestasis of pregnancy

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