Abstract：
Primary hyperparathyroidism (PHPT) includes sporadic PHPT and hereditary PHPT. However, until now, there have been no exact data on the proportion and composition of hereditary PHPT in the Chinese PHPT population. This study aimed to clarify the proportion and composition of hereditary PHPT in patients at a large academic center in Beijing, China, and to analyze genotype-phenotype characteristics. A total of 394 newly diagnosed Han PHPT patients who consented to genetic screening were enrolled. Targeted next-generation sequencing (T-NGS) (including for MEN1, RET, CDKN1B, CaSR, HRPT2/CDC73, GNA11, AP2S1, GCM2), combined with MEN1-multiplex ligation-dependent probe amplification (MLPA) and CDC73-MLPA, was used for genetic screening. Diagnosis of hereditary PHPT was based on clinical manifestations, family history, and genetic screening. Thirty-seven pathogenic (P)/likely pathogenic (LP) variants were detected in 41 patients via T-NGS, and three patients carried long-range deletions of MEN1 or CDC73 detected by MLPA, with a variant detection rate of 11.2% (44/394). In total, 30 patients were clinically diagnosed with MEN1. Combined with genetic and clinical screening, the rate of hereditary PHPT in this study was 18.8% (74/394). For purposes of comparison, the rate of unequivocal nonhereditary PHPT was 66.5% (262/394); 14.7% (58/394) did not exhibit the clinical features of hereditary PHPT but carried variants of uncertain clinical significance and so could not be clearly categorized. Both the age at hospital visit (43.6 ± 14.0 versus 53.7 ± 14.9 years) and age at onset (35.4 ± 13.8 versus 50.6 ± 14.8 years) in the hereditary group (n = 74) were significantly lower than those in the nonhereditary group (n = 262). Higher levels of ionized calcium and serum β-CTX were observed in the hereditary group; proportions of parathyroid hyperplasia and multigland involvement were also higher. In addition to multigland disease and positive family history, it is recommended that patients with an age of onset less than 38 should be screened for hereditary forms. © 2023 American Society for Bone and Mineral Research (ASBMR).
摘要：
原发性甲状旁腺功能亢进(PHPT)包括散发性PHPT和遗传性PHPT。然而,直到现在,关于中国PHPT人群中遗传性PHPT的比例和组成，尚无确切数据。本研究旨在阐明在北京大型学术中心的患者中遗传性PHPT的比例和组成。中国,并分析基因型-表型特征。共纳入394例新诊断的同意基因筛查的汉族PHPT患者。靶向下一代测序（包括MEN1，RET，CDKN1B,CaSR,HRPT2/CDC73、GNA11、AP2S1、GCM2)联合MEN1-MLPA和CDC73-MLPA用于遗传筛选。遗传性PHPT的诊断基于临床表现，家族史和遗传筛查。通过T-NGS在41例患者中检测到37种P/LP变异，三名患者携带MLPA检测到的MEN1或CDC73的远程缺失，变异检出率为11.2%(44/394)。总的来说,30例患者临床诊断为MEN1。结合基因和临床筛查，本研究中遗传性PHPT的发生率为18.8%(74/394)。为了比较，明确的非遗传性PHPT的比率为66.5%(262/394);14.7%(58/394)没有表现出遗传性PHPT的临床特征，但携带VUS变异，因此，无法明确分类。入院时的年龄（43.6±14.0vs.53.7±14.9岁）和发病年龄（35.4±13.8vs.遗传组（n=74）的50.6±14.8年）显着低于非遗传组（n=262）。在遗传组中观察到较高水平的离子钙和血清β-CTX；甲状旁腺增生和多腺体受累的比例也较高。除了多腺疾病和阳性家族史，建议发病年龄小于38岁的患者应筛查遗传形式.本文受版权保护。保留所有权利。
