Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure.
Sahoko OnoJunko MatsudaEtsuko WatanabeHiroto AkaikeHideto TeranishiIppei MiyataTakanobu OtomoYoshito SadahiraTatsuki MizuochiHironori KusanoMasayoshi KageHiroo UenoKenichi YoshidaYuichi ShiraishiKenichi ChibaHiroko TanakaSatoru MiyanoSeishi OgawaYasuhide HayashiHirokazu KaneganeKazunobu OuchiPublished in: Human genome variation (2019)
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.
Keyphrases
- liver failure
- amino acid
- hepatitis b virus
- endoplasmic reticulum
- case report
- copy number
- optic nerve
- early onset
- genome wide
- single cell
- intellectual disability
- young adults
- transcription factor
- gene expression
- protein protein
- small molecule
- dna methylation
- density functional theory
- mesenchymal stem cells
- binding protein
- soft tissue
- genome wide identification
- autism spectrum disorder
- hiv infected
- molecular dynamics