Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome

  • Lee, Min Ju (Department of Pediatrics, Korea University College of Medicine) ;
  • Suh, Chae Ri (Department of Pediatrics, Korea University College of Medicine) ;
  • Shin, Jeong Hee (Department of Pediatrics, Korea University College of Medicine) ;
  • Lee, Jee Hyun (Department of Pediatrics, Korea University College of Medicine) ;
  • Lee, Yoon (Department of Pediatrics, Korea University College of Medicine) ;
  • Eun, Baik-Lin (Department of Pediatrics, Korea University College of Medicine) ;
  • Yoo, Kee Hwan (Department of Pediatrics, Korea University College of Medicine) ;
  • Shim, Jung Ok (Department of Pediatrics, Korea University College of Medicine)
  • Received : 2019.06.20
  • Accepted : 2019.08.31
  • Published : 2019.11.15
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Abstract

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive multisystemic disease that is associated with the liver, kidney, skin, and central nervous and musculoskeletal systems. ARC occurs as a result of mutations in the VPS33B (Vacuolar protein sorting 33 homolog B) or VIPAR (VPS33B interacting protein, apical-basolateral polarity regulator) genes. A female infant presented with neonatal cholestasis with a severe clinical outcome. She was diagnosed with ARC syndrome using targeted exome sequencing (TES). Exome sequencing revealed compound heterozygous mutations, c.707A>T and c.239+5G>A, in VPS33B, where c.707A>T was a novel variant; the resultant functional protein defects were predicted via in silico analysis. c.239+5G>A, a pathogenic mutation that affects splicing, is found in less than 0.1% of the general population. Invasive techniques, such as liver biopsies, did not contribute to a differential diagnosis of ARC syndrome; thus, early TES together with clinical presentations constituted an apparently accurate diagnostic procedure.

Keywords

References

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