José-Mario Capo-Chichi1, Cybel Mehawej2, Valerie Delague3, Catherine Caillaud4, Issam Khneisser5, Fadi F Hamdan6, Jacques L Michaud7, Zoha Kibar8, André Mégarbané9. 1. CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: jmcapochichi@yahoo.fr. 2. Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon. Electronic address: cybel.mehawej@usj.edu.lb. 3. Inserm, UMR_S 910, 13385 Marseille, France; Aix Marseille Université, GMGF, 13385 Marseille, France. Electronic address: valerie.delague@univ-amu.fr. 4. Service de Biochimie Médicale, Hôpital Necker Enfants Malades, Paris 75015, France. Electronic address: catherine.caillaud@inserm.fr. 5. Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon. Electronic address: issam.khneisser@usj.edu.lb. 6. CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: fadi.hamdan@recherche-ste-justine.qc.ca. 7. 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. 8. CHU Sainte-Justine Research Center, Montreal H3T 1C5, Canada. Electronic address: zoha.kibar@recherche-ste-justine.qc.ca. 9. Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon; Institut Jérôme Lejeune, Paris, France. Electronic address: andre.megarbane@usj.edu.lb.
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. CONCLUSION: 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.
BACKGROUND: Recently, biallelic mutations in the Neuroblastoma Amplified SequenceNBAS 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. CONCLUSION: 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.
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