A novel VPS33B variant identified by exome sequencing in a patient with arthrogryposis-renal dysfunction-cholestasis syndrome

Min J.U. Lee, Chae R.I. Suh, Jeong Hee Shin, Jee Hyun Lee, Yoon Lee, Baik Lin Eun, Kee Hwan Yoo, Jung Ok Shim

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)581-587
    Number of pages7
    JournalPediatric Gastroenterology, Hepatology and Nutrition
    Volume22
    Issue number6
    DOIs
    Publication statusPublished - 2019

    Keywords

    • Mutation
    • Neonatal cholestasis
    • VIPAR
    • VPS33B

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health
    • Hepatology
    • Gastroenterology

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