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Dubin-Johnson Syndrome, Genetic Testing

Dubin-Johnson syndrome (JDS) is a rare, inherited disorder characterized by a buildup of bilirubin in the liver. Bilirubin is a yellow-brown pigment formed during the normal breakdown of red blood cells. In individuals with Dubin-Johnson syndrome, there is a defect in the transport of bilirubin within liver cells, leading to its accumulation in the liver tissues. The prevalence of JDS in the general population is unknown, and the syndrome affects individuals of all ethnicities but is most common among Iranian and Moroccan Jews, with a peak prevalence of 1 case per 1.300 individuals.

Dubin-Johnson syndrome genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Key features of Dubin-Johnson syndrome include:

  • Jaundice: The most noticeable symptom is jaundice, which is a yellowing of the skin and eyes due to elevated bilirubin levels.
  • Dark urine: Bilirubin can also cause the urine to appear dark.
  • Enlarged liver: The liver may be larger than normal, but the condition does not typically lead to liver damage or impaired liver function.
  • Asymptomatic: Individuals with Dubin-Johnson syndrome may not experience significant health problems, and the condition might be discovered incidentally.

Dubin-Johnson syndrome is generally considered a benign and non-progressive condition. The jaundice associated with the disorder is usually intermittent and can be triggered by factors such as stress, illness, pregnancy, and the use of oral contraceptives.

Treatment for Dubin-Johnson syndrome is generally not required, as the condition is usually mild and does not cause significant health problems. Management may involve addressing symptoms during episodes of jaundice, but the long-term prognosis is generally favorable.

The syndrome is caused by mutations in the ABCC2 gene, which encodes a protein transporting bilirubin out of liver cells. The inheritance pattern is usually autosomal recessive, meaning that individuals with Dubin-Johnson syndrome inherit two copies of the mutated gene (one from each parent).

Diagnosis is typically confirmed through laboratory tests measuring bilirubin levels in the blood and urine. Liver biopsy may also be performed to assess the presence of pigment in the liver cells.

Dubin-Johnson syndrome is transmitted as an autosomal recessive trait caused by homozygous or compound heterozygous mutations in the ABCC2 gene. This gene encodes for the membrane transporter known as "ATP binding cassette subfamily C member 2" that mediates the flow of bilirubin-glucuronide and other organic anion conjugates from hepatocytes into bile. In addition to ABCC2, this gene is also known as cMOAT for "Canalicular Multispecific Organic Anion Transporter" or MRP2 for "Multidrug Resistance Protein 2".

The most common variant in people with JDS is c.2302 C>T or p.Arg768Trp. The p.Arg768Trp mutation in the nucleotide-binding domain prevents correct positioning and maturation of the transporter at the apical cell membrane and induces neonatal cholestasis.

The genetic test of Dubin-Johnson syndrome analyzes the 4 most frequent pathogenic mutations of the ABCC2 gene.

With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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