Introduction:: Advances in MDT working in Disorders of Sexual Development (DSD) are supported by activities which call for national and international collaborations. In the EuroDSD programme we are collecting clinical data and performing functional studies to assess the pubertal outcome of PAIS patients raised male.
Methods: Clinical information including birth phenotype, surgery, medication and pubertal outcome, from 16 post pubertal PAIS patients with known AR mutation have been collected from the UK. AR mutants were recreated and function defined by; promoter transactivation, ligand binding and N/C terminal interaction assays. Mutants R840C/H and L712F were chosen for further analysis on the basis of the functional data, poor genotype to phenotype correlation and their location at receptor surface BF3 or AF2, respectively.
Results: Clinical data suggest that EMS (external masculinisation score) at birth > 5 predicts better pubertal outcome. All of the mutations tested displayed some functional defect in at least one of the in vitro assays. Differences were observed in different cell systems, reflecting the difficulty in finding an in vitro model which reflects pubertal progression status.
Conclusion: We propose that predictions of pubertal outcome in PAIS with a known mutation can be guided by EMS at birth. More PAIS patients with the same mutation as our current cohort are needed from the UK and beyond to collect data on variability in pubertal outcome and the range of androgen doses required to complete puberty. More patients with different AR mutations are also required in order to establish correlations between functional and clinical data. The Euro DSD database which is the basis of current and future collaborative ventures currently holds 645 entries of anonymised data from 12 different countries. We gratefully acknowledge the support of BSPED members which has enabled us to contribute 179 sets of data to this valuable resource.
03 - 05 Nov 2010
British Society for Paediatric Endocrinology and Diabetes