LETTER TO THE EDITORRole of SNAP29, LZTR1 and P2RXL1 genes on immune regulation in a patient with atypical 0.5 Mb deletion in 22q11.2 region
Introduction
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is found in a heterogeneous group of disorders sharing a common genetic basis with an estimated incidence of 1:4000 live births. The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) have monosomic deletions of chromosome 22q11.2 [1]. The patients suffering from the 22q11.2DS have a common proximal breakpoint, and in 90% of patients it produces a 3 Mb deletion (typical deleted region) while in 7% of patients it produces a 1.5 Mb deletion [2]. The majority of patients with 22q11.2DS and immune defects exhibit mild to moderate deficits in T-cell numbers [3].
In 2007, D'Angelo et al. [4] reported on a molecular diagnosis of a female patient with obesity, hyperphagia, and aggressive behavior, and who had a major depressive disorder. These authors reported an atypical 1 Mb microdeletion in the 22q11.2 region, detected using the Multiplex Ligation-dependent Probe Amplification (MLPA) assay.
Therefore, the aim of this investigation was to perform a subsequent investigation using an SNP-array technique in order to better define the rearrangement and investigate the presence of other genomic imbalances in this patient. Furthermore, considering that immunological studies were not performed by D'Angelo et al. [4] we evaluate the humoral and cellular response of this rare case of atypical deletion of chromosome 22q11.2.
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Current clinical evaluation
Currently, the patient is 13 years old and on physical examination, the OFC was 57 cm (> 95th centile), height was 147 cm (< 25th centile), and weight was 122.3 kg (> 97th centile). The patient presents with hyperphagia, obesity, non-alcoholic steatohepatitis and chronic otitis media. Compulsive food eating and behavioral problems had worsened progressively. She started on antipsychotic medication to control aggressiveness and required a special education program. The patient's routine laboratory
Discussion
The risk of immunodeficiency is commonly observed in 22q11.2DS, as in patients with DGS/VCFS. However, no published studies have reported the immunological aspects of patients with atypical deletions of chromosome 22q11.2. We have conducted a study in a patient with atypical 0.5 Mb 22q11.2 deletion involving SNAP29, LZTR1, and P2RXL1 genes. The patient has elevated absolute values of T cells, TCD4+, TCD8+ and total leucocytes with an inverted CD4+/CD8+ ratio, suggesting a lymphoproliferative
Conclusion
Our results indicate that patients with a 0.5 Mb deletion in the 22q11.2 region have an immune response different from that found in patients with the typical 22q11.2DS (e.g. DGS), which is manifested as a cellular or combined immunodeficiency. Moreover, the present study suggests that SNAP29, LZTR1 and P2RXL1 genes, involved in an atypical 22q11.2 deletion, are crucial in immune regulation, particularly on expression of T, B, NK and NKT cells.
Conflict of interest statement
The author(s) declare that there are no conflicts of interest.
Acknowledgments
The authors thank the patient, their families and FAPESP (number 2010/52694-8) for financial support.
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