目的 探讨11个先天性肾上腺皮质异常患儿家系的遗传学特征。方法 选择2019年1月至2023年6月确诊的11个先天性肾上腺皮质异常患儿家系作为研究对象。应用全外显子组测序对先证者进行基因变异检测，Sanger测序及MLPA技术进行家系验证。结果 11个患儿家系经基因诊断。8例为因CYP21A2变异引起的21-羟化酶缺陷导致的先天性肾上腺皮质增生症，1例为CYP17A1变异引起的17-α羟化酶缺乏性先天性肾上腺皮质增生症，1例为STAR变异引起的脂质先天性肾上腺增生，1例为NR0B1变异引起的先天性肾上腺发育不全。CYP21A2基因共检测到7种不同的变异，这7种变异类型中频率最高的位点是c.518T>A，随后为c.293-13C>G与c.1069C>T。STAR检测到的c.780dupG与c.397C>T变异均为未报道的新变异，根据ACMG遗传变异分类标准与指南，c.780dupG位点评级为致病性变异（PVS1+PM2_Supporting+PP4），c.397C>T位点评级为临床意义未明（PM2_Supporting+PM3+PP3+PP4）。NR0B1检测到的c.64_c.65insGAGCGCGAAGC变异为未报道的新变异，该变异评级为可能致病性变异（PVS1+PM2_Supporting+PP4）。结论 对临床表型重叠的肾上腺皮质异常患儿，单凭症状和生化指标无法进行可靠鉴别，而早期基因精准诊断对确诊疾病、干预治疗、遗传咨询及生育指导至关重要。

Objective To investigate the genetic characteristics of 11 families with congenital adrenal cortex abnormalities. Methods From January 2019 to June 2023, 11 families of patients with congenital adrenal cortex abnormalities diagnosed in the Medical Genetic Center of Gansu Maternity and Child Health Hospital were enrolled. Exome sequencing was used to detect genetic variants in the proband, Sanger sequencing and MLPA were used for verify the variants and their family origin. Results 11 patient families were genetically diagnosed: 8 cases were congenital adrenal hyperplasia due to 21-hydroxylase deficiency caused by CYP21A2 variants, and 1 case was congenital adrenal hyperplasia due to 17-α hydroxylase deficiency caused by CYP17A1 variation Cortical hyperplasia, one case of lipocongenital adrenal hyperplasia caused by STAR variants, and one case of congenital adrenal hypoplasia caused by NR0B1 variants. A total of 7 different variants were detected in the CYP21A2 gene. Among the 7 variants, the site with the highest frequency was c.518T>A, followed by c.293-13C>G and c.1069C>T. The c.780dupG and c.397C>T variants of STAR are novel variants that have not been reported. According to the ACMG Genetic Variation Classification Standards and Guidelines, the c.780dupG was categorized as pathogenic (PVS1+PM2_Supporting+PP4), c.397C>T was categorized as uncertain significance (PM2_Supporting+PM3+PP3+PP4). The variant c.64_c.65insGAGCGCGAAGC of NR0B1 is a novel variant that has not been reported, which is categorized as Likely pathogenic (PVS1+PM2_Supporting+PP4). Conclusion Patients with adrenal cortex anomalies with overlapping clinical phenotypes cannot be reliably identified by symptoms and biochemical markers alone, and early precise genetic diagnosis is essential for diagnosis of the disease, interventional therapy, genetic counseling, and fertility guidance.