JOURNAL OF CLINICAL IMMUNOLOGY, vol.40, no.6, pp.883-892, 2020 (SCI-Expanded)
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 missenseCD70variation was detected (NM_001252.5:c332C>T) in concordance withCD70phenotype and familial segregation was confirmed.CD70variations 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 missenseCD70variation, 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.