title: Neuroblastoma Amplified Sequence (NBAS) mutation in recurrent acute liver failure: Confirmatory report in a sibship with very early onset, osteoporosis and developmental delay.
abstract: BACKGROUND
  Recently, biallelic mutations in the Neuroblastoma Amplified Sequence NBAS gene have been identified in ten patients that present recurrent acute liver failure (RALF) in early infancy. In addition to severe liver dysfunction, some of these individuals also suffered from other comorbidities including cardiomyopathy, neurologic phenotypes and gastrointestinal immune defects. Here we report on a consanguineous Lebanese family with three siblings affected by RALF. Of note, neonatal spontaneous fractures, developmental delay, prominent eyes, generalized hirsutism, gum hypertrophy, and hepato-splenomegaly ​were also present.
  
  
  METHODS
  Whole-genome SNP genotyping in all the patients, followed by exome sequencing was performed in one of the affected siblings.
  
  
  RESULTS
  A homozygous c.409C > T (p.Arg137Trp) missense mutation in NBAS was identified in all patients.
  
  
  CONCLUSIONS
  Overall, our findings confirm the involvement of NBAS in the pathogenesis of this condition characterized by severe liver dysfunction and help expand its phenotypical spectrum.
authors.affiliation: CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: jmcapochichi@yahoo.fr.
authors.forename: José-Mario
authors.initials: JM
authors.lastname: Capo-Chichi
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon. Electronic address: cybel.mehawej@usj.edu.lb.
authors.forename: Cybel
authors.initials: C
authors.lastname: Mehawej
authors.affiliation: Inserm, UMR_S 910, 13385 Marseille, France; Aix Marseille Université, GMGF, 13385 Marseille, France. Electronic address: valerie.delague@univ-amu.fr.
authors.forename: Valerie
authors.initials: V
authors.lastname: Delague
authors.affiliation: Service de Biochimie Médicale, Hôpital Necker Enfants Malades, Paris 75015, France. Electronic address: catherine.caillaud@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillaud
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon. Electronic address: issam.khneisser@usj.edu.lb.
authors.forename: Issam
authors.initials: I
authors.lastname: Khneisser
authors.affiliation: CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: fadi.hamdan@recherche-ste-justine.qc.ca.
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Hamdan
authors.affiliation: CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada; Department of Pediatrics and Department of Neurosciences, Université de Montreal, Montreal, Canada. Electronic address: Jacques.Michaud@recherche-ste-justine.qc.ca.
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
authors.affiliation: CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: zoha.kibar@recherche-ste-justine.qc.ca.
authors.forename: Zoha
authors.initials: Z
authors.lastname: Kibar
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon; Institut Jérôme Lejeune, Paris, France. Electronic address: andre.megarbane@usj.edu.lb.
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007223:Infant; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D010024:Osteoporosis / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D035781:Siblings; D055815:Young Adult
chemical_list: C117339:NBAS protein, human; D009363:Neoplasm Proteins
keywords: NBAS; Recurrent acute liver failure; Spontaneous bone fractures