CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants. Issue 1 (6th November 2017)

• Record Type: Journal Article
• Authors: Simonetti, Leandro; Bruque, Carlos D.; Fernández, Cecilia S.; Benavides‐Mori, Belén; Delea, Marisol; Kolomenski, Jorge E.; Espeche, Lucía D.; Buzzalino, Noemí D.; Nadra, Alejandro D.; Dain, Liliana
• Is Part Of: Human mutation. Volume 39:Issue 1(2018)
• Page Start: 5
• Page End: 22
• Publication Date: 2017-11-06
• Subjects: 21‐hydroxylase deficiency -- congenital adrenal hyperplasia -- CYP21A2 -- genetic variants -- genotype–phenotype correlation; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23351
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis. Disorders in steroid 21‐hydroxylation account for over 95% of patients with CAH. Clinically, the 21‐hydroxylase deficiency has been classified in a broad spectrum of clinical forms, ranging from severe or classical, to mild late onset or non‐classical. Known allelic variants in the disease causing CYP21A2 gene are spread among different sources. Until recently, most variants reported have been identified in the clinical setting, which presumably bias described variants to pathogenic ones, as those found in the CYPAlleles database. Nevertheless, a large number of variants are being described in massive genome projects, many of which are found in dbSNP, but lack functional implications and/or their phenotypic effect. In this work, we gathered a total of 1, 340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have an effect on human health, and compiled all this information in an integrated database. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations, including double mutants in cis. Data compiled in the present work could help physicians in the genetic counseling of families affected with 21‐hydroxylase deficiency. Abstract : Disorders in steroid 21‐hydroxylation account for over 95% of patients with Congenital Adrenal Hyperplasia. We gathered a total of 899 unique genetic variants (GVs) from publicly available databases and publications for the disease causing CYP21A2 gene. From these GVs, 230 could be associated with an effect on human health. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations and compiled them in an integrated database.