Novel 3q27.2‐qter deletion in a patient with Diamond–Blackfan anemia and immunodeficiency: Case report and review of literature

Abstract

3q27.2-qter deletion syndromes feature an overlapping set of terminal and interstitial deletions with variable congenital malformations. Diamond-Blackfan anemia (DBA) is etiologically heterogeneous disorder in which one cause is dominant mutations of the RPL35A gene on 3q29. We report a child with a 3q27.2-qter deletion that contains the RPL35A gene. She had clinical and laboratory features consistent with DBA and as well, an unexplained immunodeficiency disorder. Given these unusual findings, we reviewed other patients in the literature with overlapping genomic deletions. In addition, we evaluated our patient for the immunodeficiency disorder, RIDDLE syndrome, due to recessive mutations in the RNF168 gene on 3q29. A PubMed search for case reports of 3q27.2-qter overlapping deletions was performed. To determine if RPL35A was in the deletion region, the chromosomal regions reported were mapped to genomic regions using the UCSC Genome Browser. We identified 85 overlapping deletions, of which six included the RPL35A gene and all should be had DBA. Interestingly, none of the reported cases had immunodeficiency. To evaluate RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties), we sequenced the remaining RNF168 gene and examined her fibroblast culture for a DNA double strand break repair deficiency. These results were normal, indicating that the immunodeficiency is unlikely to result from a RNF168 deficiency. We show that RPL35A haploinsufficiency is a cause of DBA and we report a novel case with 3q27.2-qter deletion and immunodeficiency. The etiology for the immunodeficiency remains unsolved and could be caused by an unknown gene effect or consequent to the DBA phenotype.

Innate immune system activation in zebrafish and cellular models of Diamond Blackfan Anemia

“…On the other hand, some patients with ribosomopathies demonstrate features of immunodeficiency 22 , 23 . A decreased proliferation rate and translational capacity of lymphoid cells from DBA patients has been reported 24 .…”

Pure Red Cell Aplasia (PRCA) and Cerebellar Hypoplasia as Atypical Features of Polyglandular Autoimmune Syndrome Type I (APS-1): Two Sisters With the Same AIRE Mutation but Different Phenotypes

“…She represents the first case of PRCA associated with APS-1 undergoing HSCT. In literature there are no reported cases of APS-1 with cerebellar hypoplasia, but it is described in association with hereditary bone marrow failure like Fanconi anemia (15), dyskeratosis congenital (16), Diamond-Blackfan anemia (17), congenital amegakaryocytic thrombocytopenia (18), or ataxia-pancytopenia syndrome (19). Some cases of patients with cerebellitis and APS-1 are described (20); in these patients high serum and CSF titers of anti-GAD were found, with intrathecal production of such antibodies.…”