Novel variants of CYP21A2 in Vietnamese patients with congenital adrenal hyperplasia

Molecular Genetics & Genomic Medicine
Dung V ChiVan K Tran

Abstract

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. 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. 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. The result will contribute in further understanding the genotype-phenotype relationship of CAH patients and to guide better treatment and management of the affected.

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Citations

Mar 13, 2021·Molecular Diagnosis & Therapy·Paola Concolino, Rosa Maria Paragliola
Apr 18, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Wencui WangGuang Ning
Aug 4, 2021·Journal of Endocrinological Investigation·R A A MahmoudH H Elsedfy

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Methods Mentioned

BETA
PCR

Software Mentioned

SIFT
Provean
R
MutationTaster
CLC Main Workbench
DUET
Polyphen2

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