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LIG4 syndrome: clinical and molecular characterization in a Chinese cohort
- Source :
- Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-9 (2020)
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 17501172
- Volume :
- 15
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Orphanet Journal of Rare Diseases
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.951dd36bd2e34a639601715eb75f17b6
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13023-020-01411-x