Mitotic and meiotic behaviour of a naturally transmitted ring Y chromosome:: reproductive risk evaluation

Background: The mitotic and meiotic behaviour of a transmitted ring Y [r(Y)] chromosome from a father to his Klinefelter syndrome (KS) son, and the mechanism of ring formation are analysed herein. To our knowledge, this is the first reported case of natural transmission of an r(Y). Methods and Results: Amplification of X chromosome polymorphisms by PCR showed that the KS was of paternal origin. G-banding and fluorescence in situ hybridization (FISH) studies revealed a similar percentage of mosaicism in father and son by mitotic loss of r(Y). SRY gene and Y marker amplification by PCR, FISH with subtelomeric probes for Xp/Yp and Xq/Yq, and comparative genomic hybridization (CGH) analyses indicated the intactness of the Y chromosome from SRY to subtelomere Yq. FISH analysis of sperm from the father showed significantly higher frequencies (P<0.005) for diploidy and for 6, 13, 18, 21, 22, XX, XY disomies than those observed in control donors. Conclusions: An r(Y) with low material loss can be naturally transmitted, showing similar mitotic behaviour in the offspring. The presence of an r(Y) chromosome in germinal cells increased the risk of fathering offspring with numerical abnormalities, even for chromosomes not involved in the arrangement.