目的 评估新生儿基因筛查（genetic newborn screening, gNBS）在云南地区的应用价值。 方法 采用前瞻性研究方法，随机选取2021年2—12月在云南地区出生的3 001例新生儿为研究对象，采用传统新生儿筛查（traditional newborn screening, tNBS）检测生化指标，同时采用靶向二代测序技术对156种疾病相关的159个基因进行筛查。对筛查阳性新生儿进行验证和确诊试验，确诊患儿接受规范治疗和长期随访。 结果 3 001例新生儿中，基因初筛阳性者166例，占5.53%；基因携带者1 435例，占47.82%。变异频率前10位的基因为GJB2（21.29%）、DUOX2（7.27%）、HBA（6.14%）、GALC（3.63%）、SLC12A3（3.33%）、HBB（3.03%）、G6PD（2.94%）、SLC25A13（2.90%）、PAH（2.73%）和UNC13D（2.68%）。tNBS和gNBS初筛阳性新生儿中，分别确诊33例（1.10%）和47例（1.57%）患儿，gNBS+tNBS共确诊48例（1.60%）患儿。受试者操作特征曲线分析显示，tNBS、gNBS和gNBS+tNBS确诊疾病的曲线下面积（area under the curve, AUC）分别为0.866、0.982和0.968（P<0.05）。DeLong检验显示，gNBS、gNBS+tNBS的AUC高于tNBS（P<0.05）。 结论 gNBS能够扩展疾病检测范围，与tNBS联合应用，可显著缩短诊断时间，实现尽早干预治疗。

Objective To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. Methods A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. Results Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). Conclusions gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.