Phenotype-genotype Correlations of CYP21A2 Mutations in Patients with Congenital Adrenal Hyperplasia in Turkey

Şimşek E., Binay Ç., Çilingir O., Demiral M., Hazer I., Artan S.

57th Annual European Society for Paediatric Endocrinolog, Athens, Greece, 27 - 29 September 2018, pp.140

  • Publication Type: Conference Paper / Summary Text
  • City: Athens
  • Country: Greece
  • Page Numbers: pp.140
  • Eskisehir Osmangazi University Affiliated: Yes


Background: Mutations in the 21-hydroxylase gene (CYP21A2) accounts for 90–95% of all congenital adrenal hyperplasia (CAH) cases. There is a strong relationship between genotype and disease severity.

Objective: The aim of the study was to investigate the most frequent known mutations in CYP21A2 and to describe the genotype-phenotype correlation in Turkish children with CAH due to 21-hydroxylase deficiency.

Methods: Based on clinical and hormonal criteria, patients were classified according to phenotype as salt-wasting (SW), simple-virilising (SV) or nonclassical (NC). Genetic analysis was performed using a reverse-hybridisation strip-based assay (the CAH StripAssay) that explored the presence of the 11 CYP21A2 mutations most prevalent in European populations: P30L, I2 splice (IVS2), Del 8 bp E3 (G110del8nt), I172N, Cluster E6 (I236N, V237E, M239K), V281L, L307 frameshift (F306+T), Q318X, R356W, P453S and R483P.

Results: Of the 46 patients included in the study, the disease-causing CYP21A2 gene mutations were found in 25 (54%) across all three forms of CAH. The most frequent mutations were point mutations (84%), followed by splice site mutations (24%) and deletions (4%). In the SW group, three patients were homozygous and one heterozygous for I2 splice, one was homozygous for P30L+I2splice+del 8bp+E3 del, one was homozygous for I2splice+Q318X and one was heterozygous for I2splice+V281L. In the SV group, one patient was homozygous for I172N and one was heterozygous for I172N+Q318X. In the NC group, seven patients were heterozygous for Q318X, seven were heterozygous for V281L, one was heterozygous for V281L+P453S and one was heterozygous for I172N.

Conclusion: Hormonal assays can diagnose CAH, but they are unable to discriminate heterozygotes from normal individuals or detect disease severity. This study showed a good correlation between genotype and phenotype in patients with 21-hydroxylase deficiency. The results suggest that well-known mutations can predict disease severity.