Case Report: Three novel pathogenic ABCC2 mutations identified in two patients with Dubin–Johnson syndrome

Zhao, Chenyu; Shi, Xiaoliu; Zhang, Yonghong; Huang, Hui

doi:10.3389/fgene.2022.895247

Cited by 3 publications

(5 citation statements)

References 22 publications

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“…Recent studies have confirmed that the ABCC2 gene mutation is responsible for the loss of MRP2 function, which causes DJS in affected patients. [1][2][3]5].…”

Section: Discussionmentioning

confidence: 99%

“…Dubin-Johnson syndrome (DJS) is an autosomal recessive inherited disorder that causes high levels of conjugated bilirubin and changes the way the body processes coproporphyrins, leading to increased urinary excretion of coproporphyrin I relative to coproporphyrin III. DJS is caused by a mutation in the ATP Binding Cassette Subfamily C Member 2 (ABCC2) gene, which codes for the multi-drug resistance protein 2 (MRP2) bilirubin transporter and is primarily present in the canalicular membrane of hepatocytes [ 1 , 2 ]. In 1954, Dubin and Johnson documented 12 cases of persistent idiopathic jaundice with an unidentified pigment in the liver as a new clinical and pathological entity [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The prevalence of DJS is estimated to be less than one case per 100,000 individuals globally, but it is more common among Iranian Jews. Although it is considered a rare disorder worldwide, the incidence of the condition among Sephardic Jews is approximately 1 in 3000, according to reports [ 1 , 2 ]. Many individuals with DJS are typically young adults and do not display any symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Dubin-Johnson Syndrome: A Case Report

Siddiqui¹,

Alsabe²,

Tehseen³

et al. 2023

Cureus

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Dubin-Johnson syndrome (DJS) is a rare autosomal recessive genetic disease caused by mutations in the bilirubin transporter MRP2. It is characterized by recurrent episodes of jaundice and conjugated hyperbilirubinemia. Numerous instances of hyperbilirubinemia disorders resembling Dubin-Johnson syndrome have been documented, but they differ in the clinical presentation, amount of conjugated bilirubin present, and their reaction to therapy. Most people with this syndrome do not have any symptoms, so their cases are often misdiagnosed and not properly taken care of. Here, we present a case of a teenage male patient who complained of recurring jaundice and abdominal pain. Further examination and testing revealed that the patient had been jaundiced since birth and had a family history of the condition. Conservative management was implemented, and follow-up demonstrated a positive prognosis. This case is a rare example of Dubin-Johnson syndrome, although patients with the condition generally have a normal life expectancy and only require conservative management.

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“…Recent studies have confirmed that the ABCC2 gene mutation is responsible for the loss of MRP2 function, which causes DJS in affected patients. [1][2][3]5].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dubin-Johnson Syndrome: A Case Report

Siddiqui¹,

Alsabe²,

Tehseen³

et al. 2023

Cureus

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“…In a study by Zhao et al, two patients diagnosed with DJS were studied. Whole-exome sequencing was conducted, and three variants (c.2980delA, c.1834C > T, and c.4465_4473delinsGGCCCACAG) were identified [11]. In a case report by Kamal et al, molecular testing for the ABCC2 gene using quantitative polymerase chain reaction was used for diagnosis, and c.2273G > T, pG785V in exon 18 was identified [12].…”

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin–Johnson Syndrome: A Case Report

Kim

Kang

Kim

et al. 2022

IJMS

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We report a case of a patient with Dubin–Johnson syndrome confirmed by a genetic study. A 50-year-old woman who had symptoms of intermittent right upper quadrant abdominal pain was diagnosed with calculous cholecystitis at another institute and was presented to our hospital for a cholecystectomy. She had no history of liver disease, and her physical examination was normal. Abdominal computed tomography showed a gallbladder stone with chronic cholecystitis. During a laparoscopic cholecystectomy for cholecystitis, a smooth, black-colored liver was noted, and a liver biopsy was performed. The biopsy specimen showed coarse, dark brown granules in centrilobular hepatocytes via hematoxylin and eosin staining. We performed a genetic study using the blood samples of the patient. In the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) mutation study, a missense mutation in exon 18 was noted. Based on the black-colored liver without nodularity, conjugated hyperbilirubinemia, the liver biopsy results of the coarse pigment in centrilobular hepatocytes, and the ABCC2 mutation, Dubin–Johnson syndrome was diagnosed. The patient was managed with conservative care using hepatotonics. One month after follow-up, total bilirubin and direct bilirubin remained in a similar range. Another follow-up was planned a month later, and the patient maintained her use of hepatotonics.

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“…[4,5] At the heart of DJS is the AR inheritance of mutations in the ABCC2 gene, a key player in the transport of bilirubin and other organic anions from the liver into bile. [6,7] The authors have no funding and conflicts of interest to disclose.…”

Section: Introductionmentioning

confidence: 99%

Clinical characteristics and follow-up of a newborn with Dubin–Johnson Syndrome: A clinical case report

Zhang,

Zuo,

Gao

2024

Medicine

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Background: Dubin–Johnson syndrome (DJS) is a rare autosomal recessive liver disorder, characterized by conjugated hyperbilirubinemia. This case report investigates the clinical characteristics and longitudinal outcomes of a neonate diagnosed with DJS. Methods: A newborn presented with elevated bilirubin levels and abnormal liver enzyme readings. Comprehensive genetic evaluation was conducted, which included peripheral blood sample collection from the infant and both parents after obtaining informed consent and high-throughput trio exome sequencing was performed. The genetic analysis revealed 2 significant mutations in the ABCC2 gene on chromosome 10: the insertion mutation c.4237(exon30)_c.4238(exon30)ins CT, inherited from the father, and the missense mutation c.517(exon5)G > A, inherited from the mother. Both mutations were classified as pathogenic according to the ACMG 2015 guidelines, indicating a compound heterozygous inheritance pattern. The patient’s treatment regimen included phototherapy, which was initiated to address her jaundice upon admission. To support liver function and regulate gut activity, oral ursodeoxycholic acid (20 mg/kg/dose, twice a day) and probiotics were administered. Additionally, a postdischarge medication plan involving a low-dose regimen of phenobarbital (3.5 mg/kg/dose, twice a day) was implemented for 2 weeks. Results: During a 2-year follow-up after discharge, the infant’s bilirubin levels significantly decreased, and liver enzymes, including GGT, progressively normalized. Conclusion: This case report enhances the understanding of DJS in neonates by emphasizing the clinical ramifications of compound heterozygous mutations within the ABCC2 gene and documenting the evolution of the disease. The gradual normalization of liver function tests suggests potential compensatory mechanisms in response to the genetic abnormalities in neonates with DJS. The correlation between the patient’s genetic profile of compound heterozygosity and her milder clinical phenotype warrants attention, suggesting that this specific genetic configuration may be associated with less severe manifestations of the disease. The necessity for long-term follow-up is highlighted, recognizing that intercurrent stress conditions could influence the hepatic profile and potentially exacerbate symptoms. Such sustained observation is crucial to further delineate the genomic and clinical landscape of DJS, offering opportunities to refine prognostic and therapeutic approaches.

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Case Report: Three novel pathogenic ABCC2 mutations identified in two patients with Dubin–Johnson syndrome

Cited by 3 publications

References 22 publications

Dubin-Johnson Syndrome: A Case Report

Dubin-Johnson Syndrome: A Case Report

Genotype–Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin–Johnson Syndrome: A Case Report

Clinical characteristics and follow-up of a newborn with Dubin–Johnson Syndrome: A clinical case report

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