Male infertility caused by a de novo partial deletion of the DAZ cluster on the Y chromosome

Deletions in distal Yq interval 6 represent the cause of 10-15% of idiopath ic severe male infertility and map to a region defined AZFc (azoospermia fa ctor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatog enesis. However, DAZ is actually a multicopy gene family consisting of seve n clustered copies spanning about 1 megabase. Only deletions removing the e ntire DAZ gene cluster together with other genes have been reported in infe rtile males. Because no case of spermatogenic failure has been traced to in tragenic deletions, point mutations, or even deletions not involving all th e DAZ copies, the definitive proof for a requirement of DAZ for spermatogen esis is still debatable. Here we report the first case of a partial deletio n of the DAZ cluster removing all but one of the copies. This deletion is p resent in a patient affected with severe oligozoospermia who had a testicul ar phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile b rother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.