SLCO1B1 and SLCO1B3 genetic mutations in Taiwanese patients with Rotor syndrome

Ya-Yuan Cheng; Kai-Chi Chang; Pei-Lung Chen; Chun-Yan Yeung; Bang-Yu Liou; Huey-Ling Chen

doi:10.1016/j.jfma.2023.03.003

SLCO1B1 and SLCO1B3 genetic mutations in Taiwanese patients with Rotor syndrome

J Formos Med Assoc. 2023 Jul;122(7):648-652. doi: 10.1016/j.jfma.2023.03.003. Epub 2023 Mar 23.

Authors

Ya-Yuan Cheng¹, Kai-Chi Chang², Pei-Lung Chen³, Chun-Yan Yeung⁴, Bang-Yu Liou⁵, Huey-Ling Chen⁶

Affiliations

¹ School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
² Department of Pediatrics, National Taiwan University Children's Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, Taiwan.
⁵ Department of Pediatrics, National Taiwan University Children's Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁶ Department of Pediatrics, National Taiwan University Children's Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Education and Bioethics, National Taiwan, University College of Medicine, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: hueyling@ntu.edu.tw.

PMID: 36964102
DOI: 10.1016/j.jfma.2023.03.003

Abstract

Rotor syndrome is a rare, benign, inherited disorder that is commonly associated with mild hyperbilirubinemia. It is caused by bi-allelic pathological variants in both SLCO1B1 and SLCO1B3 genes, causing defective OATP1B1 and OATP1B3 in the sinusoidal membrane and interrupted bilirubin uptake of the hepatocytes. We report five Taiwanese pediatric and adult patients aged 5-32 years presenting with conjugated hyperbilirubinemia, and were found to have genetic variants of SLCO1B1 and SLCO1B3. Two also had history of prolonged neonatal jaundice. Genetic analysis using panel-based next generation sequencing revealed three patients with homozygous mutations c.1738C>T (p.R580∗) in SLCO1B1 and a transposon LINE-1 insertion in SLCO1B3, one patient with homozygous mutations for another haplotype, c.757C>T (p.R253∗) in SLCO1B1 and c.1747+1G>A in SLCO1B3. Another patient had heterozygous c.1738C>T (p.R580∗) in SLCO1B1 linked with a LINE-1 insertion in SLCO1B3, and heterozygous c.757C>T (p.R253∗) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3. In conclusion, we present the first time of genetic diagnosis of Rotor syndrome in Taiwan. Advanced genetic testing has enhanced the diagnosis of rare diseases with mild symptoms.

Keywords: Genetic diagnosis; High-throughput nucleotide sequencing; Hyperbilirubinemia; Jaundice; Rotor syndrome.

MeSH terms

Adult
Child
Humans
Hyperbilirubinemia
Hyperbilirubinemia, Hereditary* / genetics
Infant, Newborn
Liver-Specific Organic Anion Transporter 1 / genetics
Mutation
Organic Anion Transporters* / genetics
Organic Anion Transporters, Sodium-Independent / genetics
Solute Carrier Organic Anion Transporter Family Member 1B3 / genetics

Substances

Organic Anion Transporters, Sodium-Independent
Organic Anion Transporters
Liver-Specific Organic Anion Transporter 1
Solute Carrier Organic Anion Transporter Family Member 1B3
SLCO1B1 protein, human
SLCO1B3 protein, human