Perspectives and Editorials: Letter to the Editor

Abstract

To the Editor: We read with great interest the article by Hadjkacem-Lukil et al (2007), which suggested the 4 sequence-tagged site (STS) markers sY84, RBMY, sY130, and sY157 for diagnostic testing of Yq microdeletions in a Tunisian population. We would like to point out some flaws in their study which could be interesting to your readers. First, they reported 2 patients with absence of sY255 and presence of sY254. We determined the repeat number and relative position of both markers using the UCSC in silico polymerase chain reaction tool on the male-specific region of the human Y chromosome (MSY) reference sequence (Skaletsky et al, 2003; UCSC Genome Browser, http:genome.ucsc.edu). The DAZ gene family contains 4 nearly identical copies (Saxena et al, 2000), and there is at least 1 copy of each STS inside each DAZ copy. As clearly depicted in the Figure, the minimum deleted region due to absence of sY255 also removes all copies of the sY254 marker. . Schematic representation of DAZ genes and relative position of sY255 and sY254 markers. When only sY254 is absent, at least 1 putative breakpoint must occur inside of DAZ1 or DAZ4 genes; however, such deletions could not be explained by any proposed mechanism for deletion of azoospermia factor (AZF) c by homologous recombination (P5/distal P1, P4/distal P1, and b2/b4). Second, they reported 10 patients who were negative for Y254 and positive for sY255. Negative results for either sY255 or sY254 indicated a large deletion that removes all copies of the DAZ genes. According to the European Academy of Andrology and the European Molecular Genetics Quality Network (EAA/EMQN) guidelines, deletion of just 1 of these 2 markers must always be considered a technical flaw (Simoni et al, 2004). Third, they introduced sY84 and sY157 markers for diagnosis of microdeletions in azoospermia factor (AZF) a and AZF c regions, respectively. However, at least 2 STS loci in each AZF region should be analyzed to reinforce diagnostic accuracy (Simoni et al, 2004). Fourth, analysis of their result showed that the frequency of microdeletion among oligozoospermic men was higher than azoospermic men. However, on the basis of a meta-analysis by Foresta et al (2001), azoospermic men had a higher incidence of microdeletions than oligozoospermic patients. Microdeletions could rarely be found in oligozoospermic men with sperm concentration between 1 and 5 × 106/mL (Simoni et al, 2004). Fifth, they introduced the 3 markers, sY86, sY127, and sY134 (which are actually recommended by EAA/EMQN guidelines), as polymorphic STSs. Analysis of their results showed that 18% (16 of 89) of normozoospermic men had Yq microdeletions, whereas on the basis of meta-analysis by Foresta et al (2001), the frequency of microdeletions in fertile men was estimated to be about 0.4% (12 of 2663).