Functional Characterization of Novel ATP7B Variants for Diagnosis of Wilson Disease

Frontiers in Pediatrics
Sarah GuttmannHartmut H Schmidt

Abstract

Background: Diagnosis of rare Wilson disease (WD) in pediatric patients is difficult, in particular when hepatic manifestation is absent. Genetic analysis of ATP7B represents the single major determinant of the diagnostic scoring system in WD children having mild symptoms. Objectives: To assess the impact of molecularly expressed ATP7B gene products in order to assist diagnosis of Wilson disease in pediatric patients having a novel mutation and subtle neuropsychiatric disease. Methods: The medical history, clinical presentation, biochemical parameters, and the genetic analysis of ATP7B were determined. Due to ambiguous clinical and biochemical findings and identification of a novel compound ATP7B mutation with unknown disease-causing status, a molecular analysis of the ATP7B gene products in a previously well characterized cell model was performed. Results: The ATP7B variants were transgenically expressed and the respective gene function molecularly characterized. Despite normal mRNA expression, low ATP7B protein expression of the mutants p.L168P and p.S1423N was observed (34.3 ± 8% and 66.0 ± 8%, respectively). Copper exposure did not result in decreased viability of transgenic cells as compared to wild type. Intracellular cop...Continue Reading

References

Dec 5, 1998·American Journal of Human Genetics·J R Forbes, D W Cox
Nov 4, 2000·The Journal of Pediatrics·D C WilsonE A Roberts
Oct 26, 2001·The Journal of Biological Chemistry·Ruslan TsivkovskiiSvetlana Lutsenko
Apr 30, 2003·Journal of Pediatric Gastroenterology and Nutrition·Raffaele IorioAngela Vegnente
Sep 6, 2003·Liver International : Official Journal of the International Association for the Study of the Liver·Peter FerenciFrieder Berr
Sep 28, 2004·Journal of Pediatric Gastroenterology and Nutrition·Raffaele IorioUNKNOWN Hepatology Committee of Italian Society of Paediatric Gastroenterology Hepatology and Nutrition
Mar 19, 2005·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Anil DhawanGiorgina Mieli-Vergani
Jan 21, 2006·The Journal of Pediatrics·Silvia CapraiGiuseppe Maggiore
Feb 14, 2006·Gastroenterology·Michael A CaterJulian F B Mercer
Feb 6, 2007·Lancet·Aftab AlaMichael L Schilsky
Apr 17, 2007·Gastroenterology·Peter FerenciWolfgang Stremmel
May 29, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eve A RobertsUNKNOWN American Association for Study of Liver Diseases (AASLD)
Jan 3, 2009·Journal of Hepatology·Hartmut H-J Schmidt
Jun 30, 2009·Parkinsonism & Related Disorders·Marina SvetelVladimir S Kostić
Nov 26, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Peter V E van den BergheLeo W J Klomp
Oct 23, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emanuele NicastroRaffaele Iorio
Feb 22, 2012·Journal of Hepatology·UNKNOWN European Association for Study of Liver
Mar 23, 2013·Brain : a Journal of Neurology·Alison J CoffeyOliver Bandmann
Aug 22, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Walter O ArrudaHélio A G Teive
Jun 4, 2014·PloS One·Gursimran ChandhokHartmut H J Schmidt
Aug 29, 2014·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Michelle JesseDilip Moonka
Dec 1, 2013·Journal of Clinical and Experimental Hepatology·Mallikarjun PatilHarshad Devarbhavi
Jun 3, 2015·Molecular and Cellular Neurosciences·Min ZhuZhi-Ying Wu
Jul 15, 2015·Pediatric Gastroenterology, Hepatology & Nutrition·Md Rukunuzzaman
Oct 17, 2015·Pediatric Gastroenterology, Hepatology & Nutrition·Jung Ah KimHan-Wook Yoo
Jan 1, 2016·Journal of Pediatric Gastroenterology and Nutrition·Ekkehard SturmBenjamin L Shneider
Mar 16, 2016·Biochimica Et Biophysica Acta·Ivona DjuricThomas Weide
Apr 2, 2016·Journal of Cell Science·Vasiliki LaliotiIgnacio V Sandoval
Apr 29, 2016·World Journal of Gastroenterology : WJG·Gursimran ChandhokHartmut Hj Schmidt
Sep 8, 2016·Metallomics : Integrated Biometal Science·Svetlana Lutsenko
Jul 29, 2017·Journal of Pediatric Gastroenterology and Nutrition·Anna WiernickaPiotr Socha

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Methods Mentioned

BETA
biopsy
Assay
PCR
cesarean section

Software Mentioned

SPSS

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