Evaluation of SHOX copy number variations in patients with Mullerian aplasia

Background: Mullerian aplasia (MA) characterized by congenital loss of functional uterus and vagina is one of the most difficult disorders of female reproductive health. Despite of growing interest in this research field, the cause of the disorder for the majority of patients is still unknown. A recent report of partial SHOX duplications in five patients with MA has motivated us to further evaluate their role in the disorder. Therefore we have studied SHOX copy number variations (CNVs) in a cohort of 101 Finnish patients with MA and in 115 healthy controls. Methods: We used multiplex ligation-dependent probe amplification (MLPA) to study SHOX CNVs. Results: All patients showed normal amplification of SHOX. Several aberrations, duplications and deletions, were found downstream of the gene in five patients and seven controls, but these were all copy number polymorphisms. Conclusions: Our study in an extensive cohort of patients with MA does not support a role for SHOX CNVs in the aetiology of the disorder. Further studies in the field are important for both patients looking for answers as well as for the scientific community for better understanding the regulation of the female reproductive duct development.