儿童/青少年起病的特发性甲状旁腺功能减退症患者拷贝数变异研究OA北大核心CSTPCD

Objective To screen for copy number variation(CNV)in a large cohort of childhood/adolescent-onset idiopathic hypoparathyroidism(IHP)in a single center,and to explore the correlation between CNV and the clinical phenotype of HP.Methods The study included patients with childhood/adolescent-onset IHP who were followed at the Department of Endocrinology,Peking Union Medical College Hospital from 1975 to 2021.Normal controls were matched according to gender ratio.Clinical data were collected retrospectively.CNV(≥100 kb)were detected through low-depth whole-genome sequencing.The occurrence rate and burden of CNV in IHP patients were compared with those of controls.Differences in HP-related clinical phenotype were also compared among CNV-positive and CNV-negative groups,as well as among IHP patients with different CNV burdens.Results A total of 125 IHP patients underwent CNV analysis,among which 55 cases(44.0%)were CNV-positive,with 23 patients carrying more than two CNVs.Among the 20 normal controls,six(30%)were CNV-positive,with no significant differences in the occurrence rate and burden of CNV between IHP pa-tients and controls(P＞0.05).In addition,there were no significant difference in HP-related clinical phenotype between CNV-positive and CNV-negative groups(P＞0.05),except for the post-treatment urine calcium levels in children;nor among patients with different burdens of CNV(P＞0.05).One IHP patients carried pathogenic and another patient carried likely pathogenic CNVs,but no CNV-related phenotypes were observed.Conclusion A significant correlation between CNV(≥100 kb)and IHP or its clinical phenotype was not found in this study.Larger sample size and different methodolo-gies might be required to explore the potential role of CNV of various sizes in the pathogenesis of IHP.