Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLMgene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20–80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR.
Tijdig de diagnose stellen voordat groeihormoontherapie wordt overwogenHet Bloom-syndroom (BS) is een zeldzame DNA-reparatiestoornis. Dit beeld kan op jonge leeftijd herkend worden aan de hand van de meest kenmerkende symptomen: pre- en postnatale groeiachterstand en...Lees meer
Bloom Syndrome in Short Children Born Small for Gestational Age: A Challenging Diagnosis Background: GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is...Lees meer
Abstract DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. The majority of these syndromes are inherited in an autosomal- recessive manner, but...Lees meer
Stichting Bloom Syndrome
Nistelrode, The Netherlands