Identification of pathogenic mutations from nonobstructive azoospermia patients†

It is estimated that approximately 25% of nonobstructive azoospermia (NOA) cases are caused by single genetic anomalies, including chromosomal aberrations and gene mutations. The identification of these mutations in NOA patients has always been a research hot spot in the area of human infertility. However, compared with more than 600 genes reported to be essential for fertility in mice, mutations in approximately 75 genes have been confirmed to be pathogenic in patients with male infertility, in which only 14 were identified from NOA patients. The small proportion suggested that there is much room to improve the methodology of mutation screening and functional verification. Fortunately, recent advances in whole exome sequencing and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 have greatly promoted research on the etiology of human infertility and made improvements possible. In this review, we have summarized the pathogenic mutations found in NOA patients and the efforts we have made to improve the efficiency of mutation screening from NOA patients and functional verification with the application of new technologies. We reviewed the recent advances in the identification of pathogenic mutations for nonobstructive azoospermia (NOA) and introduced how we have identified new mutations from NOA patients in our recent studies.