Exploring the Involvement of RSPO1 Gene Variations in 46,XX DSD Patients With Mullerian Agenesis and/or Gonadal...

There is a dearth of knowledge on the genetic background of Indian 46,XX DSD patients with Mullerian agenesis (MA) and/or gonadal dysgenesis (GD). Being one of the key controlling genes in female sex determination/differentiation, there is a paucity of study regarding the association of RSPO1 variations with MA/GD. Hence in this study, we screened proximal as well as exonic regions of the RSPO1 gene in 25 Indian 46,XX DSD patients with MA and/or GD.

Bidirectional PCR-Sanger sequencing was performed with RSPO1 proximal promoter and coding sequence-specific primers. The identified noncoding and coding variations were analyzed using various population and microRNA databases and in silico tools.

We observed three promoters (c.-1189C>G;rs10908365, c.-1112G>A;rs59740072, and c.-1038T>C;rs11585920), two 5' UTRs (c.-247C>G;rs187926864 and c.-119G>A;rs530760760), four intronic (c.286+33G>A;rs12039431, c.286+34C>T;rs12046650, c.95-34C>G;rs45577433, and c.94+37G>A), and a missense variant (c.484A>C;p.Lys162Gln) in our study subjects. In pathogenic prediction, the identified variations were found to be normal.

Although no clearly pathogenic RSPO1 variants were identified, this study contributes important data on RSPO1 sequence variation in 46,XX DSD cases involving MA and GD.