Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing

Molecular and Cellular Probes
S M HerbstJ Vermehren

Abstract

Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal rece...Continue Reading

References

Sep 1, 1991·Gut·G Mieli-VerganiA P Mowat
Apr 29, 1998·Journal of Pediatric Gastroenterology and Nutrition·M ThomsonD Kelly
Feb 13, 2001·Journal of Paediatrics and Child Health·M O StormonK J Gaskin
Sep 25, 2002·Transplantation Proceedings·E PfisterM Melter
Apr 27, 2004·Human Mutation·Carsten BergmannKlaus Zerres
Feb 9, 2005·Kidney International·Carsten BergmannUNKNOWN APN (Arbeitsgemeinschaft für Pädiatrische Nephrologie)
Oct 28, 2008·Human Mutation·Sharon E PlonUNKNOWN IARC Unclassified Genetic Variants Working Group
Jan 10, 2009·Orphanet Journal of Rare Diseases·Anne Davit-SpraulEmmanuel Jacquemin
Apr 28, 2010·Seminars in Liver Disease·Anne Davit-SpraulEmmanuel Jacquemin
Jun 5, 2010·Journal of Medical Genetics·Caroline Gaudy-MarquesteAnnachiara De Sandre-Giovannoli
Aug 5, 2010·Journal of Pediatric Gastroenterology and Nutrition·Ursula MatteJorge A Bezerra
Aug 5, 2010·Journal of Pediatric Gastroenterology and Nutrition·Henrik ArnellBjörn Fischler
Nov 10, 2012·Nature Biotechnology·Amy S GargisIra M Lubin
Apr 16, 2013·Gastroenterology·Gideon M HirschfieldAndrew L Mason
Jul 28, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Heidi L RehmUNKNOWN Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Commitee
Oct 12, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rainer BüscherPeter F Hoyer
Mar 13, 2014·Nature Genetics·Melissa SambrottaRichard J Thompson
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow

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Citations

Jan 1, 2017·Clinical Genetics·M ShagraniF S Alkuraya
Mar 10, 2017·Current Medical Research and Opinion·Christian J HendrikszStefan A Kolb
Aug 27, 2019·Pediatric Research·Neng-Li WangJian-She Wang
Feb 13, 2018·Neurology. Clinical Practice·Marc C PattersonThorsten Marquardt
Jul 22, 2017·Pediatric Gastroenterology, Hepatology & Nutrition·Su Jeong LeeSu-Kyeong Hwang
Oct 29, 2017·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Emanuele Nicastro, Lorenzo D'Antiga
Jan 30, 2019·European Journal of Pediatrics·Helena Moreira-SilvaErmelinda Santos-Silva
Mar 25, 2019·Nature Reviews. Gastroenterology & Hepatology·Amy G Feldman, Ronald J Sokol
Mar 16, 2021·Journal of Pediatric Gastroenterology and Nutrition·Saul J KarpenJames E Heubi
Jul 26, 2021·Clinics and Research in Hepatology and Gastroenterology·L López de FrutosP Giraldo

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