CLINICAL AND GENETIC FINDINGS IN A CHINESE COHORT OF PATIENTS WITH DIGEORGE SYNDROME-RELATED HYPOPARATHYROIDISM.

Objective

Patients with DiGeorge syndrome (DGS) are undiagnosed due to its diverse manifestations. We aimed to characterize the clinical manifestations in a group of Chinese patients of DGS with childhood-onset hypoparathyroidism (HP) as the primary referral, and to report a novel TBX1 mutation.

Methods

In this single-center observational study, clinical features and biochemical indices were recorded in 26 patients with DGS and 114 patients with idiopathic HP (IHP). An in vitro functional experiment was launched to analyze the novel TBX1 missense mutation.

Results

Compared with 114 patients of IHP (19.1 [13.5, 27.3] years old), 26 patients of DGS (14.9 [10.4, 20.3] years old) had the following differences: an earlier onset age of hypocalcemia; higher levels of serum parathyroid hormone, with a similar disease course; and lower doses of vitamin D preparation therapy. Among the 26 patients of DGS, only 3 of them were clinically diagnosed as this syndrome prior to genetic testing. A total of 25 patients of DGS were verified to have a TBX1 deletion and 1 case with a novel missense mutation of TBX1. The novel p.Y490C mutation in TBX1, located in the transactivation domain, was verified to decrease the transcriptional activity of the TBX1 protein.

Conclusion

In this Chinese group of patients with DGS-related HP, a relatively earlier onset age and less severity of HP were found compared to that of patients with IHP. Less common extraparathyroid manifestations are clues for the diagnosis of DGS. Additionally, our discovery of a novel TBX1 missense mutation expands the mutation database of DGS. Abbreviations: DGS = DiGeorge syndrome; HP = hypoparathyroidism; IHP = idiopathic hypoparathyroidism; LCR = low copy repeat; PCR = polymerase chain reaction; PTH = parathyroid hormone; TAD = transactivation domain.