摘要目的:探讨新生儿严重甲状旁腺功能亢进症(NSHPT)患儿的临床特征及基因变异特点。方法:选择分别于2019年8月与2022年4月在西安交通大学附属儿童医院内分泌遗传代谢科被确诊为NSHPT的患儿1、2为研究对象。采取回顾性分析方法，分析其临床病例资料，采用全外显子组测序(WES)进行基因变异检测，采用Sanger测序对候选致病变异进行家系验证结果。结果:患儿1、2主要临床特征均为生长发育迟缓、肌张力减低、高钙血症、低磷血症、高甲状旁腺激素(PTH)血症、肾脏钙盐沉积。WES结果显示患儿1存在 CASR基因c.1378-1G>A纯合剪接变异，为迄今尚未见文献报道的致病性变异；患儿2存在 CASR基因c.2038C>T纯合错义变异，为已被文献报道的可能致病性变异。Sanger测序结果显示患儿1父母均携带 CASR基因c.1378-1G>A杂合变异，患儿2父母均携带 CASR基因c.2038C>T杂合变异。 结论:2例NSHPT患儿分别存在 CASR基因c.1378-1G>A、 CASR基因c.2038C>T纯合变异，可能为导致其发生NSHPT的遗传学病因。NSHPT患儿1存在的c.1378-1G>A新变异，进一步拓展了该病患儿的 CASR基因的变异谱。

abstractsObjective:To explore the clinical features and genetic variants in two children with neonatal severe hyperparathyroidism (NSHPT).Methods:Two children who were diagnosed with NSHPT at the Children′s Hospital Affiliated to Xi′an Jiaotong University respectively in August 2019 and April 2022 were selected as the study subjects. Clinical data were collected, and both children were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing.Results:The main clinical features of the two children have included growth delay, hypotonia, hypercalcemia, hypophosphatemia, hyperparathyroid hormonemia, and renal calcium deposition. WES results showed that child 1 has harbored a homozygous c. 1378_1G>A splicing variant of the CASR gene, which was unreported previously, whilst child 2 has a harbored homozygous c. 2038C>T missense variant of the CASR gene, which was known to be likely pathogenic. Sanger sequencing confirmed that the parents of both children were heterozygous carriers. Conclusion:The homozygous c. 1378_1G>A and c. 2038C>T variants of the CASR gene probably underlay the NSHPT in the two children. Discovery of the c. 1378_1G>A variant has enriched the mutational spectrum of the CASR gene.