Copy number variations in a Chinese series of patients with DiGeorge syndrome-related hypoparathyroidism

Abstract Purpose: Large genic copy number variations (CNVs) that are rare in the general population have been identified as pathogenic variations in many human diseases. Microdeletion of chromosome 22 leads to DiGeorge syndrome-1 (DGS-1), however, research on the influence of CNVs on the phenotype of DGS-1 related hypoparathyroidism (HP) is still lacking. To understand the CNV profiles in whole genome and their correlation with HP related phenotype in a series of DGS-1 related HP patients by CNV-sequencing. Methods: CNVs were detected by low-depth whole genome sequencing. The clinical data were collected retrospectively. The HP related phenotype were compared between DGS-1 patients with and without CNV other than 22q11 deletion. Meanwhile, the incidence of CNVs and phenotype were also compared between patients with DGS-1 and idiopathic hypoparathyroidism (IHP) matched in their gender and age. Results: A total of 34 DGS-1 patients were enrolled in this CNV analysis, of whom 4 were adult-onset. The pathogenic CNV in 22q11 was confirmed in 32 (94.1%) cases. Moreover, 15 (44.1%) patients carried 22 CNVs other than 22q11.2. There was no significant difference in phenotype between patients with and without CNVs (≥100kb) other than 22q11, as well as the incidence of CNVs between DGS-1 and IHP patients. Conclusion: In our study, there seemed to be a relatively high percentage (44.1%) of patients who carried CNVs (≥100kb) other than 22q11.2, which may be related to the phenotype of DGS-1. Further analyses on larger DGS-1 related HP series, especially with normal controls from different races should be performed.