Whole-Exome Sequencing Identified a TBX6 Loss of Function Mutation in a Patient with Distal Vaginal Atresia

Study objective: The purpose of this study was to determine if there are any genetic changes with whole-exome sequencing associated with distal vaginal atresia.

Design: This was a retrospective genetics study of 5 patients who presented with distal vaginal atresia who were recruited between 2017 and 2018. Whole-exome sequencing was performed in each subject with distal vaginal atresia. Sanger sequencing was used to confirm the potential causative genetic mutation.

Setting: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Participants and main outcome measures: The main outcome measure was the rare mutations potentially associated with distal vaginal atresia in 5 patients.

Results: A truncating mutation c.266delC (p.P89Rfs*5) in the T-box transcription factor 6 (TBX6) gene, which is highly expressed in the human vagina, was identified in 1 patient using whole-exome sequencing. The deletion of the 16p11.2 region containing the TBX6 locus has also been reported previously to have the clinical feature of Müllerian agenesis. This mutation was paternally inherited by the patient. This truncating mutation was absent from all of the databases we checked, suggesting that the variant is rare and pathogenic.

Conclusion: We showed, to our knowledge, for the first time, that the mutation in TBX6 might be associated with human distal vaginal atresia.