Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children. Germline mutations in cancer-predisposition genes have been detected in approximately 10% of pediatric cancers. However, the genetic background of RMS is still unclear, especially in Asian children. DNA was extracted from the peripheral blood of children with RMS and cancer-associated genes analyzed using targeted re-sequencing. Twenty patients participated in this study. There were three deaths due to RMS. One patient developed a second neoplasm. Nine patients had long-term co-morbidities. Six pathogenic variants were found in five patients: one nonsense variant of DICER1, one exon deletion of TP53, and three missense variants of BUB1B, LIG4, and MEN1. Two of the five patients had a family history of cancer. Two patients with missense variants of LIG4 had long-term co-morbidities of drug-induced cardiomyopathy. The missense variants of LIG4, essential for DNA double-strand break repair, were detected in two unrelated patients. While this is the first report of the germline genetic analysis of Japanese children with RMS with detailed clinical information, the frequency of the variant was almost equivalent to that of previous reports from western countries. Unbiased exon sequencing may be useful to clarify the pathogenesis of RMS in children and in predicting the clinical course of these patients.

横纹肌肉瘤（RMS）是儿童最常见的软组织肉瘤之一。在大约 10% 的儿科癌症中检测到癌症易感基因的种系突变。然而，RMS 的遗传背景仍不清楚，尤其是在亚洲儿童中。从患有 RMS 的儿童的外周血中提取 DNA，并使用靶向重测序分析癌症相关基因。二十名患者参加了这项研究。RMS 导致三人死亡。一名患者出现第二个肿瘤。九名患者有长期合并症。在 5 名患者中发现了 6 个致病变异：1 个DICER1无义变异，1 个TP53外显子缺失，以及BUB1B、LIG4和3 个错义变异男子1。五名患者中有两名有癌症家族史。两名具有LIG4错义变异的患者患有药物性心肌病的长期合并症。在两名不相关的患者中检测到LIG4的错义变体，这是 DNA 双链断裂修复所必需的。虽然这是日本 RMS 儿童生殖系遗传分析的第一份报告，其中包含详细的临床信息，但该变异的频率几乎与西方国家之前的报告相当。无偏外显子测序可能有助于阐明儿童 RMS 的发病机制和预测这些患者的临床病程。