ESPE Abstracts

We present the case of a 15-year-old girl who presented with primary amenorrhoea. On examination she had absent pubertal development (Tanner Stage B1), with a normal-appearing external vagina and vaginal opening. Investigations demonstrated elevated gonadotropins, concerning for primary gonadal failure. Pelvic ultrasound and MRI demonstrated the presence of a rudimentary uterus and the absence of visible gonads. Karyotype confirmed 46 XY. Trio exome sequencing identified a missense variant of the DMRT1 gene; c.315C>G; p.(Cys105Trp). The girl’s mother was confirmed to be a mosaic carrier of the same DMRT1 mutation. Two female siblings of the index case were subsequently evaluated; one was also found to be 46 XY with a similar clinical phenotype to the index case. The other sibling was 46 XX, pre-pubertal on examination and had reassuring investigations and imaging. Doublesex- and Mab3- Related Transcription Factor 1 (DMRT1) is a gene, located on chromosome 9, which is involved in sex determination and is necessary for testicular differentiation. Mutations in this gene have previously been implicated in XY sex reversal. The mutation identified in this family has not previously been reported. Furthermore, the maternal mosaic carrier status and subsequent implications for siblings highlights the importance of screening asymptomatic family members when these mutations are identified.