Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missense CD70 variation was detected (NM_001252.5:c332C>T) in concordance with CD70 phenotype and familial segregation was confirmed. CD70 variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missense CD70 variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.

儿科癌症队列的全基因组测序研究表明，约 10% 的患者在癌症易感基因中存在种系突变。在这一群体中，由于患者对传染源的脆弱性和癌症治疗的困难，原发性免疫缺陷优先。另一方面，对这些疾病的早期识别可能会提供特定的靶向治疗和造血干细胞移植作为一种选择。除了治疗益处外，早期诊断还将为家庭成员提供遗传咨询。在此背景下，通过外显子组测序对具有多次近亲婚姻的大家庭和患有联合免疫缺陷（CID）和/或霍奇金淋巴瘤表型的受影响个体进行了检查。检测到与CD70表型一致的致病性纯合错义CD70变异 (NM_001252.5:c332C>T)，并确认了家族分离。 CID 和恶性肿瘤患者的CD70变异很少有报道。本文报道了一个大家庭，其中多名成员患有 CID 和携带错义CD70变异的恶性肿瘤，并回顾了文献中报道的罕见病例。原发性免疫缺陷似乎是儿童癌症的潜在原因。更好地关注这些先天性疾病以预防或早期诊断恶性转化并降低死亡率非常重要。