Dr Melissa Robinson^1
1Mater Pathology, Brisbane, Australia

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that leads to impaired corticosteroid synthesis. Three overlapping phenotypes can be seen - salt-wasting, simple virilising and non-classic; the phenotype can be attributed to the amount of functional enzyme produced. The phenotype can often be predicted from the least severe genetic variant. 

 

Next Generation Sequencing (NGS) is a cost effective testing methodology, commonly used in large reproductive carrier screening panels. However, there are caveats to the information available from short-read NGS. Certain genes have low depth of coverage and/or may be difficult to map to the reference genome. This can be due to highly repetitive sequence regions, or significant homology with a pseudogene. CYP21A2 is one such gene, due to the presence of the CYP21A2P pseudogene. Testing of this gene is further complicated by variable numbers of the active gene and pseudogene per allele. 

 

This talk will use clinical cases to demonstrate some of the complex alleles that can be identified in CYP21A2. The limitations of performing this testing on NGS and when to consider full CYP21A2 screening.