Clinical features and genetic analysis of three patients with Infantile liver failure syndrome type 2 due to variants of NBAS gene
10.3760/cma.j.cn511374-20240711-00385
- VernacularTitle:NBAS基因变异所致婴儿肝衰竭综合征2型3例患儿的临床及遗传学研究
- Author:
Suli LI
1
;
Zhidan YU
;
Xuan ZHENG
;
Bingjie QUAN
;
Yijing LIU
;
Shiyue MEI
;
Fang ZHOU
Author Information
1. 郑州大学附属儿童医院 河南省儿童医院 郑州儿童医院消化科，郑州 450018
- Publication Type:Journal Article
- Keywords:
Infantile liver failure syndrome type 2;
NBAS gene;
Mutation
- From:
Chinese Journal of Medical Genetics
2025;42(1):56-63
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
