Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency
Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency
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DOI：
10.1016/j.clim.2015.07.004
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发表时间：
2015-10-01
影响因子：
8.6
通讯作者：
Kanazawa, Nobuo
中科院分区：
文献类型：
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作者：
Tamura, Shinobu;Higuchi, Kohei;Kanazawa, Nobuo
我们在此描述一个17岁的男孩，患有顽固性寻常疣、身材矮小、小头畸形和缓慢进展的全血细胞减少症。T细胞受体重组切除环（TREC）和免疫球蛋白κ缺失重组切除环（KREC）的同时定量表明T细胞和B细胞的生成非常差。通过全外显子组测序，在患者的DNA连接酶IV（LIG 4）基因中发现了新的复合杂合突变。LIG 4综合征的诊断通过来自患者的经γ辐照的成纤维细胞中的延迟DNA双链断裂修复动力学以及通过引入野生型LIG 4的恢复来证实。虽然患者接受了来自其半相合母亲的异基因造血干细胞移植，但由于免疫系统重建不充分，他不幸死亡。因此，使用TREC/KREC定量和全外显子组测序的早期明确诊断将允许早期干预，这对于改善在青少年中隐藏的缓慢进展的LIG 4综合征的类似病例的长期生存至关重要。(C)2015 Elsevier Inc. All rights reserved.
We herein describe a case of a 17-year-old boy with intractable common warts, short stature, microcephaly and slowly-progressing pancytopenia. Simultaneous quantification of T-cell receptor recombination excision circles (TREC) and immunoglobulin kappa-deleting recombination excision circles (KREC) suggested very poor generation of both T-cells and B-cells. By whole exome sequencing, novel compound heterozygous mutations were identified in the patient's DNA ligase IV (LIG4) gene. The diagnosis of LIG4 syndrome was confirmed by delayed DNA double-strand break repair kinetics in gamma-irradiated fibroblasts from the patient and their restoration by an introduction of wild-type LIG4. Although the patient received allogeneic hematopoietic stem cell transplantation from his haploidentical mother, he unfortunately expired due to an insufficiently reconstructed immune system. An earlier definitive diagnosis using TREC/KREC quantification and whole exome sequencing would thereby allow earlier intervention, which would be essential for improving long-term survival in similar cases with slowly-progressing LIG4 syndrome masked in adolescents. (C) 2015 Elsevier Inc. All rights reserved.