title: Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy.
abstract: Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever.
authors.affiliation: Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Haack
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Staufner
authors.affiliation: Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Marlies G
authors.initials: MG
authors.lastname: Köpke
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Beate K
authors.initials: BK
authors.lastname: Straub
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
authors.affiliation: Children's Hospital Reutlingen, 72764 Reutlingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.affiliation: Department of Pediatrics, University Hospital Center Zagreb and University of Zagreb, School of Medicine, 10000 Zagreb, Croatia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Baric
authors.affiliation: Liver Unit, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McKiernan
authors.affiliation: Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dikow
authors.affiliation: Department of Neuroradiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Harting
authors.affiliation: Ophthalmology Department, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Flemming
authors.initials: F
authors.lastname: Beisse
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Burgard
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Urania
authors.initials: U
authors.lastname: Kotzaeridou
authors.affiliation: Children's Hospital Karlsruhe, 76133 Karlsruhe, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kühr
authors.affiliation: Children's Hospital St. Elisabeth, 56564 Neuwied, Germany.
authors.forename: Urban
authors.initials: U
authors.lastname: Himbert
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Distelmaier
authors.affiliation: University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.affiliation: University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Ghaloul-Gonzalez
authors.affiliation: Division of Human Genetics, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Kremer
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Graf
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzmayr
authors.affiliation: Computational Genomics, Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bader
authors.affiliation: Computational Genomics, Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieland
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Caterina
authors.initials: C
authors.lastname: Terrile
authors.affiliation: Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.affiliation: Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany. Electronic address: prokisch@helmholtz-muenchen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
mesh_terms: D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D059472:Exome / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005787:Gene Frequency; D005858:Germany; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D017114:Liver Failure, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D012008:Recurrence; D017422:Sequence Analysis, DNA
chemical_list: C117339:NBAS protein, human; D009363:Neoplasm Proteins