Pediatr Gastroenterol Hepatol Nutr.  2019 Nov;22(6):581-587. 10.5223/pghn.2019.22.6.581.

A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome

Affiliations
  • 1Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. shimjo@korea.ac.kr

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.

Keyword

Neonatal cholestasis; VIPAR; VPS33B; Mutation

MeSH Terms

Biopsy
Cholestasis
Computer Simulation
Diagnosis, Differential
Exome*
Female
Humans
Infant
Kidney
Liver
Musculoskeletal System
Protein Transport
Skin
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