Chen A, Tiosano D, Guran T, Baris HN, Bayram Y, Mory A, Shapiro-Kulnane L, Hodges CA, Coban Akdemir Z, Turan S, Jhangiani SN, van den Akker F, Hoppel CL, Salz HK, Lupski JR, Buchner DA. Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency. Hum Mol Genet. 2018 Mar 16. PMID: 29566152.
From the abstract: "Primary ovarian insufficiency (POI) is characterized by amenorrhea and loss or dysfunction of ovarian follicles prior to the age of 40. ... the genetic etiology of POI most often remains unknown. Here we report MRPS22 homozygous missense variants ... identified in four females ... as a novel genetic cause of POI in adolescents. Both missense mutations identified in MRPS22 are rare, occurred in highly evolutionarily conserved residues, and are predicted to be deleterious to protein function. .... Furthermore, we demonstrate in a Drosophila model that mRpS22 deficiency specifically in somatic cells of the ovary had no effect on fertility, whereas flies with mRpS22 deficiency specifically in germ cells were infertile and agametic, demonstrating a cell autonomous requirement for mRpS22 in germ cell development. These findings collectively identify that MRPS22 ... is critical for ovarian development and may therefore provide insight into the pathophysiology and treatment of ovarian dysfunction."