Detection of microdeletions involving the DAZ locus in idiopathic male infertility

ABSTRACT

Deletions of the AZFc [azoospermic factor c] region of the Y chromosome including DAZ gene are the most common known cause of spermatogenic failure. This study was conducted with the aim of detecting Y chromosome microdeletions involving the DAZ locus in idiopathic male infertility to allow rapid and accurate diagnosis required for proper genetic counseling. The study included 30 male patients with idiopathic azoospermia [24/30] or oligozoospermia [6/30]. A control group consisted of 10 normal fertile males and 5 females. All cases were subjected to detailed history, clinical examination, assessment of testicular volume, semen analysis, serum hormonal profile [FSH, LH, testosterone], testicular biopsy, chromosome analysis, polymerase chain reaction [PCR] amplification of two specific loci of the DAZ gene on the Y chromosome [sY254 and sY255], single strand conformations polymorphism analysis [SSCP]. The result of the study revealed that deletions involving the sY245 and sY255 DAZ loci were found in 4 cases [4/30; 13.3%]; 3 azoospermic patients and one with severe oligozoospermia. All four cases with microdeletions had decreased testicular volume, normal serum LH and T, serum FSH was elevated in 3 of them and normal in one. The two loci were amplified normally in the male control group and failed to amplify in the female control group. SSCP analysis failed to find any point mutations in sY254 and sY255 in patients with absence of microdeletions of DAZ gene. In conclusion, the estimated frequency of microdeletions involving the DAZ locus is 13.3% in azoospermic and severely oligozoospermic Egyptian men with idiopathic infertility. Polymerase chain reaction amplification of the DAZ locus is a rapid and accurate method for the diagnosis of microdeletions of the Y chromosome in patients with idiopathic infertility especially those seeking micromanipulation assisted reproduction