NANOS3 and Primary amenorrhea: In conclusion, we report a rare homozygous missense mutation in NANOS3 in two Brazilian sisters with primary amenorrhea from a cohort of 85 Brazilian women with POI. In vitro and in silico functional studies support that this inactivating mutation abolishes NANOS3 ability to prevent apoptosis, suggesting a mechanism for POI involving increased PGC apoptosis during embryonic cell migration.