Abstract for presentation at 11th International Congress of Human Genetics

Mutational Spectrum of steroid 21-hydroxylase in Australian patients with congenital adrenal hyperplasia: GeneMapper analysis and identification of 6 novel mutations

  • Mr Ivan McGown, Mater Laboratory Services, Sth Brisbane, Australia
  • Ms Yvette Jeske, Mater Laboratory Services, Sth Brisbane, Australia
  • Dr David Cowley, Australia
  • Dr Catherine Choong, Department of Paediatric Endocrinology & Diabetes, Mater Heatlh Services, Sth Brisbane, Australia
  • Dr Andrew Cotterill, Department of Paediatric Endocrinology & Diabetes, Mater Heatlh Services, Sth Brisbane, Australia

    • Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by a deficiency of one of the five enzymes involved in the biosynthesis of cortisol. About 90-95% of CAH cases are caused by decreased steroid 21-hydroxylase activity. In this study we have tested 65 unrelated Australian patients with classical and non-classical forms of congenital adrenal hyperplasia (CAH) and 30 of their respective family members. Novel GeneMapper analysis detected large gene deletions/conversions in 32% of the 130 unrelated CAH alleles. Patients had a wide variety of wild-type gene (CYP21) to pseudogene (CYP21P) ratios, ranging from multiple CYP21 copies (4:1) to having no CYP21 genes and many CYP21P genes (0:4). This highlights the complexity involved when performing CYP21 genotyping. Direct sequencing of the 10 exons of the CYP21 gene revealed in descending order the following common point mutations derived from the pseudogene by micro gene conversion: Intron 2 splice site (33%), I172N (11%), Q318X (4%), V281L (3%) and P30L (3%). Six novel mutations were found in five patients: five point mutations (D43N, D106G, L433P, G447X, and P463L) and one small deletion (Cys 173 7bp deletion). Mutations were detected in 95% of the unrelated alleles. This is the first report of the mutational spectrum of the CYP21 gene in Australia.

    Conference Organiser - ICMS Pty Ltd