Targeted next-generation sequencing reveals two novel mutations of NBAS in a patient with infantile liver failure syndrome-2

Mutations in neuroblastoma amplified sequence (NBAS) cause infantile liver failure syndrome-2 (ILFS2). NBAS is a protein involved in Golgi-to-endoplasmic reticulum retrograde transport. Exon capture in combination with high-throughput sequencing was used to detect NBAS mutations. Via targeted sequencing, two causative mutations were identified from 358 selected genes associated with growth and development diseases; one was a missense mutation, c.3596G>A (p.C1199Y), detected in the coding region of NBAS (NM_015909.3), and the other a splice site mutation, c.209+1G>A. Both of these were heterozygous. The SEC39 structure of the wild-type NBAS protein was compared with a model of the mutated protein. The overall structure of the SEC39 after mutation did not change; however, steric hindrance did increase. In conclusion, two novel NBAS mutations were identified in a 4-year-old Chinese girl with ILFS2.