A patient with mutations in DNA ligase IV: Clinical features and overlap with Nijmegen breakage syndrome
A patient with mutations in DNA ligase IV: Clinical features and overlap with Nijmegen breakage syndrome
复制标题
DOI：
10.1002/ajmg.a.30869
复制
发表时间：
2005-09-01
影响因子：
2
通讯作者：
Nezarati, MM
中科院分区：
文献类型：
--
作者：
Ben-Omran, TI;Cerosaletti, K;Nezarati, MM
Ligase IV综合征(LIG4综合征)是一种极其罕见的常染色体隐性遗传病，由LIG4基因突变引起，其临床表型与奈梅根断裂综合征(NBS)非常相似，以小头畸形、特征性面部特征、生长迟缓、发育迟缓和免疫缺陷为特征。我们报告一位4(1)/(2)岁男童，表现为急性T细胞白血病。面部的格式塔让人强烈地联想到国家广播公司。这名患者在T细胞白血病开始治疗后不久死亡。随后的染色体断裂研究表明，在成纤维细胞培养中，染色体断裂的比率很高。放射敏感性通过集落存活试验进行评估；结果显示，放射敏感性高于NBS的典型情况。NBS1基因突变筛查为阴性。对LIG4基因进行测序，发现2440C>；T(R814X)为纯合子截断突变。虽然这种突变以前在LIG4综合征中被发现，但这位患者是第一例报告的该突变的纯合子。在这项研究中，我们回顾了这种罕见综合征的临床特征，并提出了鉴别诊断的建议。(C)2005年Wiley-Liss，Inc.
The clinical phenotype of Ligase IV syndrome (LIG4 syndrome), an extremely rare autosomal recessive condition caused by mutations in the LIG4 gene, closely resembles that of Nijmegen breakage syndrome (NBS), and is characterized by microcephaly, characteristic facial features, growth retardation, developmental delay, and immunodeficiency. We report a 4(1)/(2)-year-old boy who presented with acute T-cell leukemia. The facial gestalt was strongly reminiscent of NBS. The patient died shortly after the onset of treatment for his T-cell leukemia. Subsequent chromosome breakage studies showed a high rate of breakage in a fibroblast culture. Radiosensitivity was assessed by a colony survival assay; the results showed radiosensitivity greater than is typically seen in NBS. Mutation screening of the NBS1 gene was negative. Sequencing of the LIG4 gene revealed a homozygous truncating mutation 2440 C > T (R814X). Although this mutation has been previously noted in LIG4 syndrome, this patient is the first reported homozygote for the mutation. In this study, we review the clinical features of this rare syndrome and provide suggestions for differential diagnosis. (c) 2005 Wiley-Liss, Inc.