T-Cell and Parathyroid Dysfunction in Conotruncal Cardiac Defects: Relationship to 22q11 deletion. • 121

Abstract

Recent observations of deletion in chromosome 22q11 in patients with conotruncal heart defects (CHD) has led to suggestions that these patients belong to the CATCH 22 group of defects. Subtle abnormalities of T-cell numbers and low levels of parathormone (PTH) are frequently seen in patients with CHD. The details of the relationship of T-cell and parathyroid dysfunction, occurring in patients with CHD, to 22q11 deletion is not fully established. We studied 34 patients with CHD. The surface markers of peripheral lymphocytes were identified by flow cytometry and CD3, CD4, CD8, CD16, and CD19 positive cells were counted. PTH was measured by radioimmunoassay. Fluorescent in situ hybridization using probe D22S75 was performed on the metaphase chromosome spreads. As this probe may not detect a smaller deletion in 22q11, genotyping of the patient and parents (where available) were done using 5 microsatellites to probe for smaller deletions involving these loci. Four microsatellites mapped to the DiGeorge critical region on 22q11 (D22S941, D22S944, D22S311, D22S264), and 1 mapped to the 10p region, deletion of which is also associated with DiGeorge syndrome (D10S585). Eight patients had deletions in 22q11 based on D22S75. One other patient had a deletion involving the locus D22S944, but not D22S311 or D22S264. No patient had a deletion in the 10p region. The number of patients in the categories of CD3 count 15% (CD3+ cells which are both CD4- and CD8-, normal <10%) and low PTH (<10pg/ml) are as follows:Table In conclusion, reduction in T-cell numbers and PTH levels occur frequently in patients with CHD, irrespective of a detectable deletion in 22q11, consistent with the notion of overlap between patients with CHD and CATCH 22. Some of these patients may have a smaller deletion in 22q11, as demonstrated in one of our patients, or even a point mutation in one of the critical genes. High numbers of double negative T-cells have not been described in CATCH 22 previously, and may further indicate disordered T-cell differentiation.