21-hydroxylase genotyping in Australasian patients with congenital adrenal hyperplasia.
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.
Jeske
Y W A
YW
Mater Children's Hospital, Brisbane, QLD.
McGown
I N
IN
Harris
M
M
Bowling
F G
FG
Choong
C S Y
CS
Cowley
D M
DM
Cotterill
A M
AM
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*
D013255:Steroid 21-Hydroxylase