An audit of a mutation screening service for the 21-hydroxylase gene
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic disorders, which result in a deficiency of enzymes in the cortisol synthesis pathway. The majority (>90%) of CAH is caused by 21-hydroxylase enzyme deficiency (21OH).
In response to concerns about the management of CAH patients in the UK an audit of CAH referrals to the laboratory was conducted. A total of 495 CAH families referred for molecular testing of the CYP21 gene between January 2000 and June 2005 were examined. Overall the review of the CAH service has lead to improvements to the 21-hydroxylase deficiency mutation detection service through new technology. It has also identified a requirement for further information on the molecular genetics of CAH and a possible need for a review of the current carrier risk of 1 in 50. Liaising with clinical genetics and endocrinology we hope to create up to date information of CAH. [N.Gregersen et al. 2006. In progress].
One area the audit highlighted was the correlation between genotype and phenotype. In patients where two mutated alleles had been identified we compared the expected mutation effect to the phenotype of the patient. The phenotype was as predicted from the identified genotype in 80.7% of cases. It was also noted that in 31% of patients only one mutation had been identified. To increase our detection rate we have developed a rapid test, using pyro-sequencing, for another relatively common mutation in CYP21, the exon 6 cluster mutation (g.1380T>A and g.1383T>A). To date we have identified 12% (5/42) of patients, where only one mutation had previously been identified, as positive for the exon 6 cluster mutation. This new test avoids the need for sequencing the majority of the CYP21 gene, a time consuming and expensive test.