Mutations in the neuroblastoma amplified sequence (NBAS) gene correlate with infantile acute liver failure (ALF). Herein, we identified a novel NBAS mutation in a female infant diagnosed with recurrent ALF. Whole-exome and Sanger sequencing revealed that the proband carried a compound heterozygous mutation (c.938_939delGC and c.1342 T > C in NBAS). NBAS c.938_939delGC was presumed to encode a truncated protein without normal function, whereas NBAS c.1342 T > C encoded NBAS harboring the conserved Cys448 residue mutated to Arg448 (p.C448R). The proportion of CD4 + T cells decreased in the patient’s peripheral CD45 + cells, whereas that of CD8 + T cells increased. Moreover, upon transfecting the same amount of DNA expression vector (ectopic expression) encoding wild-type NBAS and p.C448R NBAS, the group transfected with the p.C448R NBAS-expressing vector expressed less NBAS mRNA and protein. Furthermore, ectopic expression of the same amount of p.C448R NBAS protein as the wild-type resulted in more intracellular reactive oxygen species and the induction of apoptosis and expression of marker proteins correlating with endoplasmic reticulum stress in more cultured cells. This study indicated that p.C448R NBAS has a function different from that of wild-type NBAS and that the p.C448R NBAS mutation potentially affects T-cell function and correlates with ALF.

神经母细胞瘤扩增序列 ( NBAS ) 基因突变与婴儿急性肝衰竭 (ALF) 相关。在此，我们在一名被诊断患有复发性 ALF 的女婴中发现了一个新的NBAS突变。全外显子组和 Sanger 测序显示先证者携带复合杂合突变（NBAS中的 c.938_939delGC 和 c.1342 T > C ）。据推测NBAS c.938_939delGC 编码了一种没有正常功能的截短蛋白，而NBASc.1342 T > C 编码的 NBAS 含有突变为 Arg448 的保守 Cys448 残基 (p.C448R)。患者外周血CD45+细胞中CD4+T细胞的比例下降，而CD8+T细胞的比例上升。此外，在转染相同数量的编码野生型 NBAS 和 p.C448R NBAS 的 DNA 表达载体（异位表达）后，转染 p.C448R NBAS 表达载体的组表达较少的NBASmRNA 和蛋白质。此外，与野生型相同数量的 p.C448R NBAS 蛋白的异位表达导致更多的细胞内活性氧物质和细胞凋亡的诱导以及与更多培养细胞中内质网应激相关的标记蛋白的表达。该研究表明 p.C448R NBAS 具有不同于野生型 NBAS 的功能，并且 p.C448R NBAS 突变可能影响 T 细胞功能并与 ALF 相关。