Premature ovarian insufficiency (POI), affecting as many as 1 in 100 women, is characterised by menstrual disturbance and elevated follicle stimulating hormone before the age of 40. The condition is highly heterogeneous with over 50 causative genes but these genes only account for ~25% of patients. POI can be associated with significant co-morbidity depending on the underlying genetic pathology. For example, POI is associated with sensorineural hearing loss in individuals with Perrault syndrome. We have used functional genomics to investigate the genetic cause of POI in a large cohort of patients, including ten cases of Perrault syndrome from seven different families. We identified novel causative variants in known Perrault syndrome genes as well as causative variants in TFAM, GGPS1, PEX6 and MRPL50, not previously associated with POI or Perrault syndrome. The role of these genes in ovarian pathology has been consolidated by the identification of additional affected families and/or functional assays in patient fibroblasts or animal models. Most identified genes responsible for Perrault syndrome have a role in mitochondrial translation or peroxisomal biogenesis/function. This highlights the need to consider ovarian function in individuals with atypical/mild mitochondrial and/or peroxisomal disorders. In one family, the affected patient presented only with POI, but genomics revealed causative variants in a Perrault syndrome gene. This demonstrates the utility of using genomics for the investigation and management of POI because co-morbidity can be predicted and the appropriate healthcare team assembled. In this case an audiologist was recruited for optimal patient management. Our genomic study highlights the diverse molecular landscape of POI and Perrault syndrome, and demonstrates the pivotal role mitochondria and peroxisomes play in ovarian function.