Cell fate decisions requiring appropriate transcriptional regulation key genes. SRY is pivotal in mammalian SD but how the expression of SRY is regulated in mammals is unknown. We identified a family from central India with 17 individuals showing variable DSD phenotypes ranging from completely sex-reversed 46,XY female to fertile males, with transmission of the phenotype linked to the Y-chromosome (Figure 4).
Figure 4. Human XY sex-reversal linked to the Y chromosome. Three pedigrees of the extended family showing Y-linked XY sex-reversal, with variable expressivity and incomplete penetrance. Genotyping defined the Y haplogroup as H1a2a1, an ancient haplogroup in India.
Genomic data indicate that this family carries a mutation in a putative enhancer element for SRY. Ongoing studies are aimed to characterise this element and understand the molecular mechanisms governing the initial switch leading to testis formation.