Conclusions
ZNF764 haploinsufficiency caused by microdeletion may be responsible for the partial multiple hormone resistance observed in our patient. ZNF764 appears to be involved in glucocorticoid, androgen, and thyroid hormone action.
Results
We found in this patient an approximately 1.1-Mb heterozygous 16p11.2 microdeletion, which included an approximately 500-kb unique deletion along with the common, previously reported approximately 600-kb 16p11.2 microdeletion. The small interfering RNA-based screening revealed that knockdown of ZNF764, which is located in the deleted segment unique to our case, significantly reduced glucocorticoid-, androgen-, and thyroid hormone-induced transcriptional activity of their responsive genes in HeLa cells, whereas its overexpression enhanced their transcriptional activity. The activities of the estrogen and progesterone receptors, cAMP response element-binding protein, and p53 were not affected in these cells. ZNF764 (zinc finger protein 764) expression was reduced in the patient's peripheral blood mononuclear cells, whereas exogenously supplemented ZNF764 recovered responsiveness to glucocorticoids in the patient's Epstein-Barr virus-transformed lymphocytes. The effect of ZNF764 on the glucocorticoid receptor transcriptional activity was mediated through cooperation with a general nuclear hormone receptor coactivator, transcriptional intermediary factor 1. Conclusions: ZNF764 haploinsufficiency caused by microdeletion may be responsible for the partial multiple hormone resistance observed in our patient. ZNF764 appears to be involved in glucocorticoid, androgen, and thyroid hormone action.