A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome
10.5223/pghn.2019.22.6.581
- Author:
Min Ju LEE
1
;
Chae Ri SUH
;
Jeong Hee SHIN
;
Jee Hyun LEE
;
Yoon LEE
;
Baik Lin EUN
;
Kee Hwan YOO
;
Jung Ok SHIM
Author Information
1. Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. shimjo@korea.ac.kr
- Publication Type:Case Report
- Keywords:
Neonatal cholestasis;
VIPAR;
VPS33B;
Mutation
- MeSH:
Biopsy;
Cholestasis;
Computer Simulation;
Diagnosis, Differential;
Exome;
Female;
Humans;
Infant;
Kidney;
Liver;
Musculoskeletal System;
Protein Transport;
Skin
- From:Pediatric Gastroenterology, Hepatology & Nutrition
2019;22(6):581-587
- CountryRepublic of Korea
- Language:English
-
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.
