title: Infantile Cirrhosis, Growth Impairment, and Neurodevelopmental Anomalies Associated with Deficiency of PPP1R15B.
abstract: To assess the utility of whole-exome sequencing (WES) in a sibling pair with undetermined liver disease and describe the phenotype associated with mutations discovered therein.
  
  
  
  Next-generation WES was performed on 2 siblings (S1 and S2) who were born to nonconsanguineous parents of European extraction. Both siblings developed cirrhosis of indeterminate etiology and required liver transplantation; S1 at 7 months and S2 at 22 months.
  
  
  
  Sequencing of germline DNA identified compound heterozygous mutations in PPP1R15B resulting in increased levels of phosphorylated eukaryotic translation initiation factor 2α.
  
  
  
  The first demonstration of PPP1R15B associated with liver disease expands the phenotypic spectrum of PPP1R15B related diseases. Our findings validate the application of WES in the diagnosis of children with undetermined liver disease. Understanding the genetic basis of liver disease may allow the development of targeted therapies for treatment and adequate counseling of families.
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Feinberg School of Medicine of Northwestern University and Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mohammad
authors.affiliation: National Institutes of Health Undiagnosed Diseases Program, Common Fund, National Institutes of Health, Bethesda, MD.
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Wolfe
authors.affiliation: Center for Genomics and Transcriptomics, Tuebingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Stöbe
authors.affiliation: Center for Genomics and Transcriptomics, Tuebingen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.affiliation: Division of Neurology, Department of Pediatrics, Feinberg School of Medicine of Northwestern University and Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wainwright
authors.affiliation: Department of Pathology, Feinberg School of Medicine of Northwestern University and Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Hector
authors.initials: H
authors.lastname: Melin-Aldana
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Feinberg School of Medicine of Northwestern University and Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Padmini
authors.initials: P
authors.lastname: Malladi
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda MD.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
authors.affiliation: Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Feinberg School of Medicine of Northwestern University and Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
mesh_terms: D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007223:Infant; D008103:Liver Cirrhosis / Q000235:genetics*; D009154:Mutation; D065886:Neurodevelopmental Disorders / Q000235:genetics*; D010641:Phenotype; D054645:Protein Phosphatase 1 / Q000172:deficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D054645:Protein Phosphatase 1
keywords: infantile cirrhosis; translation initiation factor; whole exome