Xinbao Ding, Priti Singh, Kerry Schimenti, Tina N Tran, Robert Fragoza, Jimmaline Hardy, Kyle E Orwig, Marta Olszewska, Maciej K Kurpisz, Alexander N Yatsenko, Donald F Conrad, Haiyuan Yu, John C Schimenti
Infertility is a heterogeneous condition, with genetic causes thought to underlie a substantial fraction of cases. Genome sequencing is becoming increasingly important for genetic diagnosis of diseases including idiopathic infertility; however, most rare or minor alleles identified in patients are variants of uncertain significance (VUS). Interpreting the functional impacts of VUS is challenging but profoundly important for clinical management and genetic counseling. To determine the consequences of these variants in key fertility genes, we functionally evaluated 11 missense variants in the genes ANKRD31, BRDT , DMC1, EXO1 , FKBP6, MCM9 , M1AP, MEI1, MSH4 and SEPT12 by generating genome-edited mouse models...
July 25, 2023: Proceedings of the National Academy of Sciences of the United States of America