title: 21-hydroxylase genotyping in Australasian patients with congenital adrenal hyperplasia.
abstract: Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, I2 G splice and I172N the most common. Five patients with a I172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.
authors.affiliation: Mater Children's Hospital, Brisbane, QLD.
authors.forename: Y W A
authors.initials: YW
authors.lastname: Jeske
authors.forename: I N
authors.initials: IN
authors.lastname: McGown
authors.forename: M
authors.initials: M
authors.lastname: Harris
authors.forename: F G
authors.initials: FG
authors.lastname: Bowling
authors.forename: C S Y
authors.initials: CS
authors.lastname: Choong
authors.forename: D M
authors.initials: DM
authors.lastname: Cowley
authors.forename: A M
authors.initials: AM
authors.lastname: Cotterill
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000328:Adult; D044362:Australasia; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D013255:Steroid 21-Hydroxylase / Q000097:blood / Q000235:genetics*
chemical_list: D013255:Steroid 21-Hydroxylase