ClinVar

In 2 infertile Polish men with azoospermia (SPGF12; 615413), Kusz-Zamelczyk et al. (2013) identified heterozygosity for deletion of a single serine residue (Pro77_Ser78delinsPro) from a stretch of 6 serine residues in the NANOS1 gene. The deletion was not found in 400 fertile Polish men who had at least 2 children, or in the 1000 Genomes Project database. The first patient inherited the deletion from his mother, and an infertile maternal uncle also carried the deletion; the second patient inherited the deletion from his father, indicating incomplete penetrance. In a yeast 2-hybrid assay, the mutant allele caused an approximately 14% decrease in NANOS1 interaction with GEMIN3 (DDX20; 606168). In both patients, a P34T variant in NANOS1 was also present on the mutant allele; however, P34T was present among fertile and infertile men at the same allele frequency (approximately 4.9%) and, when tested alone, did not alter NANOS1-GEMIN3 binding in the yeast 2-hybrid assay. Kusz-Zamelczyk et al. (2013) also noted that the only P34T homozygotes identified in the study were the second infertile man and his deletion-carrying father. Seminiferous tubule histology was available for the first patient and showed a Sertoli cell-only phenotype, with complete lack of germ cells.