To evaluate the prevalence of 22q11.2 deletion syndrome within a set of newborns screening positive for low T-cell receptor excision circles (TRECs) by assessing a patient’s copy number of the TBX1 and/or HIRA genes, which are located in the 22q11.2 region.

This population evaluated 486 newborns born in Taiwan who were diagnosed with low TRECs (<90 copies per microliter) on the severe combined immunodeficiency newborn screening from February 2012 to January 2015.

The newborn screening dried blood spots from the 486 patients with TREC levels <90 copies per microliter were reassessed, and the spots underwent DNA extraction. The extract was then evaluated with quantitative real-time polymerase chain reaction to assess the copy number of TBX1 and/or HIRA genes. The patients with low copy number in both genes were retested 2 times to confirm the abnormal copy number. Then, those confirmed patients had their DNA re-extracted and assessed by multiplex ligation-dependent probe amplification. This series of testing confirmed 13 cases of 22q11.2 deletion syndrome.

The results of the study showed that ∼13 cases of 22q11.2 deletion syndrome were confirmed out of the 486 patients with TREC levels <90 copies per microliter. The rate of detection was 2.7% in the entire group of patients with low TRECs. However, the positive detection rate of 22q11.2 deletion syndrome was higher at 10.7% if the patient had <30 TRECs.

Investigators in this study showed that in a group of nearly 500 Taiwanese newborns with TREC levels <90 copies per microliter, they were able to detect patients with 22q11.2 deletion syndrome through the assessment of copy numbers of TBX1 and/or HIRA genes rather than full chromosomal microarray in 2.7% by using the previously collected dried blood spot.

This confirms that TREC newborn screening can be used to find a multitude of T-cell lymphopenia problems apart from severe combined immunodeficiency. Furthermore, genes of interest can be evaluated for copy number variation as a cost-effective second tier analysis of low TRECs to further delineate patients with 22q11.2 deletion syndrome.