Objective: This study aimed to identify pathogenic variants in patients with hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome through whole-exome sequencing (WES), to elucidate the genotype-phenotype correlations, and to provide a basis for refining its clinical diagnostic criteria and genetic counseling. Methods: Three pedigrees presenting with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia, who visited the First Affiliated Hospital of Zhengzhou University between January 2022 and January 2025, were enrolled. Clinical and genetic data from the probands and their family members were systematically collected. Variant screening was performed on the probands using whole-exome sequencing (WES). Detected variants were evaluated through bioinformatic analysis, validated by Sanger sequencing for segregation within the families, and classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. A genotype-phenotype analysis of HDR syndrome was further conducted through a comprehensive literature review. Results: A total of 5 patients with HDR syndrome were diagnosed across the three pedigrees. The most common clinical phenotypes included sensorineural hearing loss (5/5), hypoparathyroidism (2/5), renal abnormalities (1/5), and preauricular fistula (1/5). Three novel pathogenic variants in the GATA3 gene were identified: c.24_27del (p.Arg9GlyfsTer2), c.681del (p.Glu228SerfsTer38), and c.759_762del (p.Lys254ProfsTer11). These variants had not been previously reported in public databases. Segregation analysis within the families confirmed their complete co-segregation with the disease phenotype, and all were classified as pathogenic according to ACMG guidelines. Conclusions: We report three novel pathogenic GATA3 variants for the first time, which expands the molecular diagnostic spectrum of HDR syndrome and provides molecular evidence for family genetic counseling and prenatal diagnosis. The combined use of WES and Sanger sequencing effectively improves the diagnostic yield for hereditary hearing loss, particularly in syndromic forms. Furthermore, a phenotype-driven targeted analysis strategy holds significant value in enhancing the detection rate of causative genes. 目的： 通过全外显子组测序（whole exome sequencing，WES）探寻甲状旁腺功能减退-感音神经性听力损失-肾发育不良（hypoparathyroidism-sensorineural deafness-renal dysplasia，HDR）综合征患者的致病变异，揭示HDR综合征的基因型-表型关联，为完善其临床诊断标准及遗传咨询提供依据。 方法： 纳入2022年1月至2025年1月就诊于郑州大学第一附属医院的3个具有甲状旁腺功能减退、感音神经性听力损失及肾脏发育异常表型的家系，系统收集先证者及家族成员的临床资料与遗传信息。通过WES技术对先证者进行变异筛查，结合生物信息学分析、Sanger测序家系共分离验证以及参照美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics，ACMG）指南进行致病性评级。通过文献回顾对HDR综合征的基因型-表型进行分析。 结果： 在3个家系中共确诊5例HDR综合征患者，常见的临床表型分别为感音神经性听力损失（5/5），甲状旁腺功能减退（2/5）、肾脏异常（1/5）及耳前瘘管（1/5）。共发现3个新型GATA3基因致病变异：c.24_27del（p.Arg9GlyfsTer2）、c.681del（p.Glu228SerfsTer38）和c.759_762del（p.Lys254ProfsTer11）。新变异既往未被数据库收录，经家系验证显示完全共分离，均被评级为致病变异。 结论： 本研究首次报道3个GATA3新致病性变异，拓展了HDR综合征的分子诊断谱系，进而为家系遗传咨询及产前诊断提供分子证据。WES联合Sanger测序能有效提升遗传性聋（尤其是综合征型）的诊断效能，临床表型导向的靶向分析策略对提高致病基因检出率具有重要价值。.

To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR). A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using "hypoparathyroidism""sensorineural deafness""renal dysplasia""HDR""Barakat" and"GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously. For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.