Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene

Abstract

We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely to contain one or more genes required for spermatogenesis (the azoospermia factor, AZF). Deletion of the AZF region is associated with highly variable testicular defects, ranging from the complete absence of germ cells to spermatogenic arrest with the occasional production of condensed spermatids. We found no evidence of YRRM genes, recently proposed as AZF candidates in the AZF region. The region contains a single-copy gene, DAZ (deleted in azoospermia), which is transcribed in the adult testis and appears to encode an RNA-binding protein. The possibility that DAZ is AZF should now be explored.