Whole Exome Sequencing Identifies a Rare Nonsense Mutation in FAM47C as a Possible Cause of Severe Oligospermia in Brothers with Varicocele

ABSTRACT Varicocele is a common cause of impaired semen parameters in men with infertility. Here, we investigated genetic variants as possible causes of varicocele with impaired semen parameters using whole-exome sequencing (WES) in a family with 2 brothers with severe oligospermia, 1 unaffected brother, father, and the mother. Results showed a premature stop codon alteration on Chromosome X (37028866 CT) in the gene FAM47C. The affected brothers were found to be hemizygous for the variant, while the mother was a heterozygous carrier. In conclusion, identifying men with varicocele that would have impaired spermatogenesis, using approaches like WES, can be paradigm shifting.