| Title: |
LIG4 syndrome: clinical and molecular characterization in a Chinese cohort |
| Authors: |
Bijun Sun, Qiuyu Chen, Ying Wang, Danru Liu, Jia Hou, Wenjie Wang, Wenjing Ying, Xiaoying Hui, Qinhua Zhou, Jinqiao Sun, Xiaochuan Wang |
| Source: |
Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-9 (2020) |
| Publisher Information: |
BMC, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
DNA ligase IV syndrome, Microcephaly, Inflammatory bowel disease, Immunodeficiency, Genetic testing, Medicine |
| More Details: |
Abstract Background DNA Ligase IV (LIG4) syndrome is a rare disease with few reports to date. Patients suffer from a broad spectrum of clinical features, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and malignancy predisposition. There may be a potential association between genotypes and phenotypes. We investigated the characteristics of LIG4 syndrome in a Chinese cohort. Results All seven patients had growth restriction. Most patients (6/7) had significant microcephaly (< − 3 SD). Recurrent bacterial infections of the lungs and intestines were the most common symptoms. One patient had myelodysplastic syndromes. One patient presented with an inflammatory bowel disease (IBD)-like phenotype. Patients presented with combined immunodeficiency. The proportions of naïve CD4+ and naïve CD8+ T cells decreased notably in five patients. All patients harbored compound heterozygous mutations in the LIG4 gene, which consisted of a missense mutation (c.833G > T, p.R278L) and a deletion shift mutation, primarily c.1271_1275delAAAGA (p.K424Rfs*20). Two other deletion mutations, c.1144_1145delCT and c.1277_1278delAA, were novel. Patients with p.K424Rfs*20/p.R278 may have milder dysmorphism but more significant IgA/IgM deficiency compared to the frequently reported genotype p.R814X/p.K424Rfs*20. One patient underwent umbilical cord blood stem cell transplantation (UCBSCT) but died. Conclusions The present study reported the clinical and molecular characteristics of a Chinese cohort with LIG4 syndrome, and the results further expand the phenotypic and genotypic spectrum and our understanding of genotype-to-phenotype correlations in LIG4 syndrome. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1750-1172 |
| Relation: |
http://link.springer.com/article/10.1186/s13023-020-01411-x; https://doaj.org/toc/1750-1172 |
| DOI: |
10.1186/s13023-020-01411-x |
| Access URL: |
https://doaj.org/article/951dd36bd2e34a639601715eb75f17b6 |
| Accession Number: |
edsdoj.951dd36bd2e34a639601715eb75f17b6 |
| Database: |
Directory of Open Access Journals |
|
Full text is not displayed to guests. |
Login for full access.
|
