Abstract:

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.

Key words: congenital adrenal hyperplasia, genetic analysis, genetic counseling, pedigree