Chromosomal aberrations as the cause of a complex phenotype in children with primary immunodeficiencies

Abstract

Most of known primary immunodeficiencies (PID) are monogenic diseases, mainly due to the point defects in the immune system genes. However, in some rare cases the immunodeficiency is caused by various chromosomal aberrations. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A retrospective analysis was performed on a group of 15 patients with clinical and laboratory signs of immunodeficiency, whose chromosomal aberrations were detected by various methods. In six patients from four different families, microdeletions with inclusion of a gene (CTLA4, NFKB1) or a part of a known PID gene (NBAS, DCLRE1C) were detected. Four patients had a complex phenotype, where a mutation in the known PID genes (BTK, CYBB, STAT1 GOF, ATM) was combined with a chromosomal defect. In one case, a homozygous damage in the USB1 gene was confirmed by detection of dysomy chromosome 16 from the father`s side. Two patients were diagnosed with known chromosomal defects -DiGeorge2 and Jacobsen syndrome. Two other patients had various chromosome abnormalities not previously described in PID`s patients. 12/15 (80%) patients had syndromic features -various skeletal dysmorphisms, malformations, and developmental delay. Immunodeficiency genes can be damaged within the chromosomal aberrations. The combination of the various methods of genetic testing is important for patients with PID. Even in PID patients without syndromic features the chromosomal analysis methods or PID diagnosis are necessary.