Ben-Omran Tawfeg I, Cerosaletti Karen, Concannon Patrick, Weitzman Sheila, Nezarati Marjan M
Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Am J Med Genet A. 2005 Sep 1;137A(3):283-7. doi: 10.1002/ajmg.a.30869.
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.
连接酶IV综合征（LIG4综合征）是一种极为罕见的常染色体隐性疾病，由LIG4基因突变引起，其临床表型与尼曼-匹克氏综合征（NBS）极为相似，特征为小头畸形、特殊面容、生长发育迟缓、发育延迟和免疫缺陷。我们报告了一名4岁半患急性T细胞白血病的男孩。其面容强烈让人联想到NBS。该患者在T细胞白血病治疗开始后不久死亡。随后的染色体断裂研究显示，其成纤维细胞培养中的断裂率很高。通过集落存活试验评估放射敏感性；结果显示其放射敏感性高于NBS患者的典型表现。NBS1基因的突变筛查结果为阴性。LIG4基因测序显示存在纯合性截短突变2440 C>T（R814X）。尽管该突变此前在LIG4综合征中已有报道，但该患者是首例报道的该突变纯合子。在本研究中，我们回顾了这种罕见综合征的临床特征并提供了鉴别诊断建议。
