Deletion of the pseudoautosomal region and lack of sex-chromosome pairing at pachytene in two infertile men carrying an X;Y translocation

Abstract

Two males with a 46, Y, der(X), t(X;Y)(p22.3;q11) complement were referred independently for evaluation of sterility with azoospermia. Both patients exhibited minimal symptomatology, characterized only by psychological disturbances. Study of X-chromosome breakpoints with pseudoautosomal probes 68B (DXYZ2 elements), 113D (locus DXYS15), and 19B (locus MIC2) indicated in both patients that at least 97% of the X pseudoautosomal sequences are lost. Hybridization with Xp22.3-specific probes DXS283, DXS284, and DXS31 shows that these loci are retained on the rearranged chromosome. Thus, the X-chromosome breakpoints are located close to the proximal boundary of the pseudoautosomal region, between MIC2 and DXS284.

A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin

“…Complete absence of pairing causes infertility associated with arrested germ cell development. 11,14,15 However, the effect of pairing failure in a single chromosome in a small proportion of cells is unknown and could be compatible with germ cell development.…”

“…Complete loss of PAR 1 in males, either through a deletion 14 or a translocation 15 results in failure of X-Y pairing. Submicroscopic deletions encompassing the SHOX gene within PAR 1 have recently been identified as the causative mutation in 12 families with Leri-Weill dyschondrosteosis (LWD), a dominantly inherited skeletal dysplasia.…”

CD99 expression is positively regulated by Sp1 and is negatively regulated by Epstein-Barr virus latent membrane protein 1 through nuclear factor-κB

“…9 The mic2 gene encoding CD99 is the first human gene isolated from the pseudo-autosomal region located at the X-and Ychromosome short arms and is required for the correct pairing of these morphologically different chromosomes during male meiosis. 10,11 Subsequent analysis of this gene defined 10 exons that are considerably smaller than average for mammalian genes. 12 At the 5Ј end of the mic2 gene, there is a GϩC-rich promoter region containing a great number of Sp1-binding core sequences with no identifiable TATA box or CAAT element, suggesting its role as a housekeeping gene.…”

Recombination Has Little Effect on the Rate of Sequence Divergence in Pseudoautosomal Boundary 1 Among Humans and Great Apes

“…PARs are regions of homology between otherwise nonhomologous sex chromosomes and undergo meiotic recombination. Pairing and crossover in the mammalian PARs may ensure proper segregation of sex chromosomes during male meiosis (Gabriel-Robez et al 1990;Mohandas et al 1992). Because obligatory meiotic crossover between the mammalian X-and Ychromosomes is confined to the short PARs, these regions undergo more intensive recombination than do adjacent Xchromosome/Y-chromosome-specific regions (Harbers et al 1986;Soriano et al 1987;Lien et al 2000).…”