A novel PPRC1 point mutation in a Chinese family with premature ovarian failure: A case study

Background: Patients with premature ovarian failure (POF) have an at least 6-month history of amenorrhea and elevated follicle-stimulating hormone levels in plasma. Most of the POF causes are idiopathic and hereditary, and chromosomal abnormalities have been associated with POF development. A pedigree study was performed on a family with idiopathic POF to observe the possible link between gene mutation and POF development.

Methods: In total, eight women were diagnosed with POF and seven POF patients and five non-POF members from the same family were evaluated by whole exome sequencing and Sanger sequencing. An apoptotic assay, senescence staining, real-time polymerase chain reaction (qPCR) and overexpression of the peroxisome proliferator-activated receptor gamma coactivator-related 1 (PPRC1) gene were performed to examine the association of POF in vitro.

Results: Through whole exome sequencing and Sanger sequencing, a novel point mutation (NM_015062: c.2902C>T:p.Thr958Ile) was identified and verified in the PPRC1 gene on chromosome 10 (10q24.32). The point mutation only presented in all the seven POF cases and not in non-POF cases or public databases. Subsequent expression of PPRC1 in COV434 granulosa cells showed that PPRC1 might be involved in regulating granulosa cell apoptosis but not senescence-associated POF development.

Conclusions: A novel point mutation in the PPRC1 gene was identified by the pedigree study and by sequence analysis of the case series with idiopathic POF in the present study. The subsequent PPRC1 expression analysis showed that PPRC1 was not involved in senescence-associated POF development. Further studies will be needed to confirm the link between PPRC1 gene mutation and POF.