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Molecular Investigations to Improve Diagnostic Accuracy in Patients With ARC Syndrome

Cited 21 time in Web of Science Cited 24 time in Scopus
Authors
Cullinane, Andrew R.; Straatman-Iwanowska, Anna; Seo, Jeong K.; Ko, Jae S.; Gizewska, Maria; Gliwicz, Dorota; Erdemir, Gulin; Wakabayashi, Yoshiyuki; Barnicoat, Angela; Gissen, Paul; Maher, Eamonn R.; Kelly, Deirdre A.; Knisely, A. S.; Garcia-Cazorla, Angels; Fischler, Bjorn; Chitayat, David; Mandel, Hanna; Hinds, Rupert; Sougrat, Rachid; Tuysuz, Beyhan; Gruszfeld, Dariusz; Song, Kyung S.
Issue Date
2009-02
Publisher
WILEY-LISS
Citation
HUMAN MUTATION; Vol.30 2; E330-E337
Keywords
arthrogryposisneonatal cholestasisvesicular trafficking defectARCrenal tubular dysfunction
Abstract
Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a multi-system autosomal recessive disorder caused by germline mutations in VPS33B. The detection of germline VPS33B mutations removes the need for diagnostic organ biopsies (these carry a >50% risk of life-threatening haemorrhage due to platelet dysfunction); however, VPS33B mutations are not detectable in similar to 25% of patients. In order further to define the molecular basis of ARC we performed mutation analysis and mRNA and protein studies in patients with a clinical diagnosis of ARC. Here we report novel mutations in VPS33B in patients from Eastern Europe and South East Asia. One of the mutations was present in 7 unrelated Korean patients. Reduced expression of VPS33B and cellular phenotype was detected in fibroblasts from patients clinically diagnosed with ARC with and without known VPS33B mutations. One mutation-negative patient was found to have normal mRNA and protein levels. This patient`s clinical condition improved and he is alive at the age of 2.5 years. Thus we show that all patients with a classical clinical course of ARC had decreased expression of VPS33B whereas normal VPS33B expression was associated with good prognosis despite initial diagnosis of ARC. (C) 2008 Wiley-Liss, Inc.
ISSN
1059-7794
Language
English
URI
http://hdl.handle.net/10371/76995
DOI
https://doi.org/10.1002/humu.20900
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College of Medicine/School of Medicine (의과대학/대학원)Pediatrics (소아과학전공)Journal Papers (저널논문_소아과학전공)
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