Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure

Abstract

Biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene have been reported to cause two different clinical spectra: short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome and infantile liver failure syndrome 2 (ILFS2). Here, we describe a case of a 3-year-old Japanese boy who presented with fever-triggered recurrent acute liver failure (ALF). The clinical characteristics were considerable elevation of liver enzymes, severe coagulopathy, and acute renal failure. In addition to the liver phenotype, he had short stature and Pelger-Huët anomaly in the peripheral granulocytes. Whole-exome and Sanger sequencing of the patient and his parents revealed that he carried novel compound heterozygous missense mutations in NBAS, c.1018G>C (p.Gly340Arg) and c.2674 G>T (p.Val892Phe). Both mutations affect evolutionarily conserved amino acid residues and are predicted to be highly damaging. Immunoblot analysis of the patient’s skin fibroblasts showed a normal NBAS protein level but a reduced protein level of its interaction partner, p31, involved in Golgi-to-endoplasmic reticulum retrograde vesicular trafficking. We recommend NBAS gene analysis in children with unexplained fever-triggered recurrent ALF or liver dysfunction. Early antipyretic therapy may prevent further episodes of ALF.

Complex Multisystem Phenotype With Immunodeficiency Associated With NBAS Mutations: Reports of Three Patients and Review of the Literature

“…Progressive reduction in NK cells numbers has been described by Garcia Segarra et al (15) and then by Ricci et al (10). As Figure 2 demonstrates, the patients who had immunodeficiency and bone disease had mutations distributed along the gene, with no particular domain predominance (10,(14)(15)(16)(17)(18)(19)(20)(21)(22)(27)(28)(29)(30)(31)(32)(33)(34)(35), current study).…”

“…mortality. Although some degree of liver disease has been associated with most NBAS variants, the mutations associated with severe liver phenotype were either loss-offunction or missense mutations predominantly located in the N-terminal and in the middle part of the NBAS gene (c.409C>T identified in 5 patients: c.680A>C;1749G>A, c.809G>C;2926del, c.1018G>C;2674G>T, c.2819A>C, and c.2819A>C) (15,18,(27)(28)(29)(30)(31).…”

Infantile fever-triggered acute liver failure caused by novel neuroblastoma amplified sequence mutations: a case report

“…NBAS mutations have also been identified in SOPH syndrome patients without liver failure [4]. An increasing number of studies have indicated that diseases based on NBAS mutations have a broad phenotypic spectrum, ranging from isolated recurrent ILFS2 to a multi-systemic disease manifesting as short stature, skeletal dysplasia, dysmorphism and optic atrophy with or without liver failure [4][5][6][7][8][9][11][12][13][14][15][16][17][18].…”

“…Previously, the mutations within the NBAS were reported to be the cause of short stature, optic atrophy and Pelger-Huët anomaly of granulocytes (SOPH) syndrome in an isolated Russian yakut population [4]. Increasing research has reported that the phenotype spectrum of NBAS mutations ranges from isolated ILFS2 to a multi-systemic disease including short stature, skeletal dysplasia and optic atrophy [5][6][7][8]. Early administration of antipyretic and support therapy can effectively ameliorate the course of ILFS2 due to NBAS mutations, improving the prognosis [8,9].…”

NBAS disease: 14 new patients, a recurrent mutation, and genotype–phenotype correlation among 24 Chinese patients

“…We systematically reviewed the liver pathologies of all patients with NBAS deficiency (previously reported patients 6,16,17,22,26,[30][31][32][33][34] and patients from our cohort). In total, 23 ALF and two non-ALF patients were enrolled.…”