A pedigree analysis of Rotor hyperbilirubinemia combined with hepatitis B virus infection in a and gene mutations patient.

BACKGROUND

Rotor syndrome (RS, OMIM#237450) is an extremely rare autosomal digenic recessive disorder characterized by mild non-hemolytic hereditary conjugated hyperbilirubinemia, caused by biallelic variation of and genes that resulted in OATP1B1/B3 dysfunction in the sinusoidal membrane leading to impaired bilirubin reuptake ability of hepatocytes.

METHODS

One RS pedigree was recruited and clinical features were documented. Whole genome second-generation sequencing was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations.

RESULTS

This study detected a homozygous nonsense variant c.1738C > T (p.R580*) in the coding region of the (NM006446) gene in a family with RS and hepatitis B virus infection by Variants analysis and Sanger sequencing, and confirmed by Copy Number Variation (CNV) analysis and Long Range PCR that there was a homozygous insertion of intron 5 of the gene into intron 5 of long-interspersed element 1 (LINE1). A few cases of such haplotypes have been reported in East Asian populations. A hepatitis B virus infection with fatty liver disease was indicated by pathology, which revealed mild-moderate lobular inflammation, moderate lobular inflammation, moderate hepatocellular steatosis, and fibrosis stage 1-2 (NAS score: 4 points/S1-2) alterations. Heterozygotes carrying p.R580* and LINE1 insertions were also detected in family members (I1, I2, III2, III3), but they did not develop conjugated hyperbilirubinemia.

CONCLUSION

The mutations may be the molecular genetic foundation for the presence of c.1738C > T(p.R580*) and (LINE1) in this RS pedigree.