ESPE Yearbook of Paediatric Endocrinology

Brief summary: This translational study showed an increased plasma expression of miR-210 in individuals with 46,XY DSD compared to the control population and also showed a positive association between the presence of atypical genitalia and plasma levels of miR-210 expression in individuals with 46,XY DSD. The findings of this study contribute to a novel perspective on the possible role of miRNAs in the development of the male external genitalia and in the development of phenotypical variability in individuals with 46,XY DSD due to same genetic defect.

Atypical external genitalia is identified in approximately 1:4500 newborns. However, more than half of affected individuals, especially the ones with 46,XY DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. Furthermore, phenotypical variability for the same allelic variant of one DSD gene in affected members of the same 46,XY DSD family is possible. These complex presentations may suggest yet unknown modulating factors regulating gene expression involved in 46,XY DSD phenotype.

MiRNAs, which are small noncoding RNAs, generally interact with the 3’UTR segment of mRNAs and subsequently inhibit protein expression. In this study, Elias FM et al. evaluated the plasma expression of miR-210 in 18 individuals with 46,XY DSD of unknown etiology compared to 36 healthy controls. MiRNA-210 was demonstrated to be differentially regulated in various male reproductive disorders. They found that plasma miR-210 expression was higher in 46,XY DSD individuals, and is positively correlated with higher EMS scores/severity of atypical genitalia independent of age, pubertal status, or hormone replacement therapy.

Although the results of this study reveal that there is increased miR-210 expression in 46, XY DSD, it is not clear with this data whether this might be a primary etiology or represent a secondary effect of abnormal male sex development.

Further investigation with a large number of 46,XY DSD individuals will be necessary to establish the role of miR-210 in the development of 46,XY DSD and variable phenotypes.