Rotor Syndrome via the SLCO1B3 Gene

Rotor syndrome is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostic compounds (van de Steeg et al. 2012). Mild jaundice begins shortly after birth or in childhood.

Rotor syndrome is an autosomal recessive disorder caused by a concurrent complete deficiency of the major hepatic drug uptake transporters OATP1B1 and OATP1B3, encoded by SLCO1B1 and SLCO1B3 genes, respectively (van de Steeg et al. 2012). This obligate two-gene disorder represents one of the clearest examples of “digenic inheritance” in human disease (Schäffer 2013). A complete deficiency of either OATP1B1 or OATP1B3 does not cause obvious jaundice (van de Steeg et al. 2012). Genetic defects of SLCO1B3 include large deletions and splicing site mutations (Human Gene Mutation Database).

Variants in the SLCO1B3 gene have been associated with hepatic clearance of substrate drugs such as xenobiotics including statins, taxanes, and mycophenolic acid (Schwarz et al. 2011). However, genotype-phenotype correlations are not yet clear. Therefore, this test is NOT for SLCO1B3-associated pharmacogenetic phenotypes.

Detection rate of pathogenic variants in the SLCO1B3 gene in a large cohort of patients with Rotor syndrome is unavailable in the literature because documented SLCO1B3 pathogenic variants have only been reported in limited cases. Of note, large deletions in the region of the SLCO1B1 and SLCO1B3 genes are apparently common in this disorder and may encompass both genes (van de Steeg et al. 2012).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the SLCO1B3 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.