High deletion frequency of the complete AZFa sequence in men with Sertoli-cell-only syndrome

We have developed a rapid screening protocol for deletion analysis of the c omplete AZFa sequence (i.e. 792 kb) on the Y chromosome of patients with id iopathic Sertoli-cell-only (SCO) syndrome. This Y deletion was mapped earli er in proximal Yq11 and first found in the Y chromosome of the SCO patient JOLAR, now designated as the AZFa reference patient. We now show that simil ar AZFa deletions occur with a frequency of 9% in the SCO patient group. In two multiplex polymerase chain reaction experiments, deletions of the comp lete AZFa sequence were identified by a typical deletion pattern of four ne w sequence-tagged sites (STS): AZFa-prox1, positive; AZFa-prox2, negative; AZFa-dist1, negative; AZFa-dist2, positive. The STS were established in the proximal and distal neighbourhoods of the two retroviral sequence blocks ( HERV15yq1 and HERV15yq2) which encompass the breakpoint sites for AZFa dele tions of the human Y chromosome. We have found deletions of the complete AZ Fa sequence always associated with a uniform SCO pattern on testicular biop sies. Patients with other testicular histologies as described in the litera ture and in this paper have only partial AZFa deletions. The current AZFa s creening protocols can therefore be improved by analysing the extension of AZFa deletions. This may provide a valuable prognostic tool for infertility clinics performing testicular sperm extraction, as it would enable the exc lusion of AZFa patients with a complete SCO syndrome.