Absence of DAZ gene mutations in cases of non-obstructed azoospermia

Sequenced-tagged site (STS) analysis of the Y chromosome long arm (Yq) ofazoospermic males has identified a minimum common deleted region of severalhundred kilobases in approximately 13% of cases. A candidate azoospermiagene, DAZ (deleted in azoospermia), has been isolated from this region. DAZhas also been shown to be absent in severely oligozoospermic males albeitat a much lower frequency. These data, although highly suggestive, do notconstitute formal proof that DAZ actually plays a role in azoospermia, asno small intragenic deletions, rearrangements or point mutations in thegene have been found. In this study we report the screening of DNA from 168azoospermic/oligospermic males for the presence of the DAZ gene. Deletionsinvolving DAZ were detected in five out of 43 (11.6%) azoospermic maleswhereas none were found in the remaining 125 oligospermic patients. Wepresent the genomic structure of the 5' end of the DAZ gene together withits sequence analysis in 30 non-obstructed azoospermic males. No mutationsin DAZ were found in any of the patients sequenced. These data provide noformal proof that DAZ is AZF. Thus the possibility is still valid thatanother gene(s) mapping to the deletion interval may be responsible for, orcontribute to, the observed phenotypes. Alternatively, if DAZ is AZF, theysuggest that the most frequent cause of gene inactivation is via largedeletions possibly mobilized by Y chromosome repetitive sequences.