Novel variants of CYP21A2 in Vietnamese patients with congenital adrenal hyperplasia

• Published in: Molecular genetics & genomic medicine 2019-05, Vol.7 (5), p.e623-n/a
• Main Authors: Chi, Dung V., Tran, Thinh H., Nguyen, Duc H., Luong, Long H., Le, Phuong T., Ta, Minh H., Ngo, Huong T. T., Nguyen, Mai P., Le‐Anh, Tuan P., Nguyen, Dat P., Bui, The‐Hung, Ta, Van T., Tran, Van K.
• Format: Article
• Language: English
• Subjects: 21OH; Adrenal Hyperplasia, Congenital - genetics; Classification; congenital adrenal hyperplasia; Congenital diseases; CYP21A2; Data analysis; Deoxyribonucleic acid; Disease; DNA; Enzymes; Gene deletion; Gene Frequency; Gene rearrangement; Gene sequencing; Genotype; Genotype & phenotype; Genotypes; Humans; Hyperplasia; mutation spectrum; novel variants; Nucleotides; Original; Pathogenicity; Pathogens; Patients; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Steroid 21-Hydroxylase - genetics; Testosterone; Vietnam
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.623

Background Congenital adrenal hyperplasia (CAH) (OMIM #201910) is a complex disease most often caused by pathogenic variant of the CYP21A2 gene. We have designed an efficient multistep approach to diagnose and classify CAH cases due to CYP21A2 variant and to study the genotype‐phenotype relationship. Methods A large cohort of 212 Vietnamese patients from 204 families was recruited. We utilized Multiplex Ligation‐dependent Probe Amplification to identify large deletion or rearrangement followed by complete gene sequencing of CYP21A2 to map single‐nucleotide changes and possible novel variants. Results Pathogenic variants were identified in 398 out of 408 alleles (97.5%). The variants indexed span across most of the CYP21A2 gene regions. The most common genotypes were: I2g/I2g (15.35%); Del/Del (14.4%); Del/I2g (10.89%); p.R356W/p.R356W (6.44%); and exon 1–3 del/exon 1–3 del (5.44%). In addition to the previously characterized and documented variants, we also discovered six novel variants which were not previously reported, in silico tools were used to support the pathogenicity of these variants. Conclusion The result will contribute in further understanding the genotype‐phenotype relationship of CAH patients and to guide better treatment and management of the affected. This is a mutation study in a large cohort of 212 patients with congenital adrenal hyperplasia (CAH) in Vietnam, in which we discovered six novel disease causing variants of CYP21A2. This is the first mutation study of CAH in Vietnam and the result should help in further understanding the genotype‐phenotype relationship of CAH and will guide better treatment and management of the disorder.