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

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.

• Authors: Min Ju Lee, Chae Ri Suh, Jeong Hee Shin, Jee Hyun Lee, Yoon Lee, Baik-Lin Eun, Kee Hwan Yoo, Jung Ok Shim
• Journal: Pediatric gastroenterology, hepatology & nutrition (Pediatr Gastroenterol Hepatol Nutr) Vol. 22 Issue 6 Pg. 581-587 (Nov 2019) ISSN: 2234-8646 [Print] Korea (South)
• PMID: 31777725 (Publication Type: Case Reports)
• Copyright: Copyright © 2019 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.