Dubin-Johnson syndrome; Chronic idiopathic jaundice - ABCC2 gene
Dubin-Johnson syndrome, also known as chronic idiopathic jaundice, is an alteration characterized by yellowing of the skin and the sclera. In most affected people, jaundice appears during adolescence or early adulthood, although some individuals have been diagnosed shortly after birth. In these cases, affected newborns have hepatomegaly and cholestasis that disappear later. Although jaundice is usually the only symptom of Dubin-Johnson syndrome, some people also present with weakness, mild upper abdominal pain, nausea and / or vomiting.
Dubin-Johnson syndrome is due to mutations in the ABCC2 gene (ATP binding cassette subfamily C member 2), located on the long arm of chromosome 10 (10q24.2). This gene encodes the multidrug resistance protein 2 (MRP2). This protein acts as a pump to transport substances outside the liver, kidneys, intestine, or placenta so that they can be excreted from the body.
More than 40 mutations in the ABCC2 gene responsible for Dubin-Johnson syndrome have been identified. Most of these mutations change amino acids in the MRP2 protein. A common mutation among Iranian Jews living in Israel replaces the amino acid isoleucine with the amino acid phenylalanine at position 1173 in MRP2 (Ile1173Phe or I1173F). Another mutation that is frequently observed among the Moroccan-Jewish population of Israel replaces the amino acid arginine with the amino acid histidine at position 1150 in MRP2 (Arg1150His or R1150H). Mutations in the gene result in a version of the protein that cannot efficiently pump substances out of cells. These mutations affect in particular the transport of bilirubin in the bile. As a result, bilirubin accumulates in the body, leading to hyperbilirubinemia, which causes the yellow color of the skin and the sclera in people with the disease.
This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have the mutations so that the alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Dubin-Johnson syndrome, by means of the complete PCR amplification of the exons of the ABCC2 gene, and their subsequent sequencing.
Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).