Recombination in the pseudoautosomal region in a 47,XYY male

Abstract

Males with a 47,XYY karyotype generally have chromosomally normal children, despite the high theoretical risk of aneuploidy. Studies of sperm karyotypes or FISH analysis of sperm have demonstrated that the majority of sperm are chromosomally normal in 47,XYY men. There have been a number of meiotic studies of XYY males attempting to determine whether the additional Y chromosome is eliminated during spermatogenesis, with conflicting results regarding the pairing of the sex chromosomes and the presence of an additional Y. We analyzed recombination in the pseudoautosomal region of the XY bivalent to determine whether this is perturbed in a 47,XYY male. A recombination frequency similar to normal 46,XY men would indicate normal pairing within the XY bivalent, whereas a significantly altered frequency would suggest other types of pairing such as a YY bivalent or an XYY trivalent. Two DNA markers, STS/STS pseudogene and DXYS15, were typed in sperm from a heterozygous 47,XYY male. Individual sperm (23,X or Y) were isolated into PCR tubes using a FACStarPlus flow cytometer. Hemi-nested PCR analysis of the two DNA markers was performed to determine the frequency of recombination. A total of 108 sperm was typed with a 38% recombination frequency between the two DNA markers. This is very similar to the frequency of 38.3% that we have observed in 329 sperm from a normal 46,XY male. Thus our results suggest that XY pairing and recombination occur normally in this 47,XYY male. This could occur by the production of an XY bivalent and Y univalent (which is then lost in most cells) or by loss of the additional Y chromosome in some primitive germ cells or spermatogonia and a proliferative advantage of the normal XY cells.

A patient with 47, XYY mosaic karyotype and congenital absence of bilateral vas deferens: a case report and literature review

“…In theory, X, Y, XY, YY should be observable in the sperm of such patients, and there should be a 50% chance of abnormal karyotypes occurring in their offspring. However, studies have reported that chromosomal abnormalities are rare in the offspring of such patients, and the incidence is less than 1% [ 9 , 10 ]. Although the risk of infertility for this syndrome is four times higher than that of ordinary men, most patients are fertile.…”

“…The animal model that sterile triploid chromosome mice can obtain fertile offspring through the phenomenon of “trisomy bias chromosome loss” also strongly supports this view [ 10 ]. Studies have shown that the sperm count of patients with 47, XYY syndrome is uncertain, and the sperm count ranges from average to azoospermia [ 9 , 11 ]. Moreover, 46, XY/47, XYY chimera can produce normal sperm; most people are fertile, as we reported in this patient.…”

“…Regarding these patients, percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection (ICSI) may help increase their fertility. The in vitro fertilization and embryo cleavage rates are high, and the fetuses born are also very healthy [ 9 , 10 ].…”

New developments and future trajectories in supernumerary sex chromosome abnormalities: a summary of the 2022 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and XYY

“…Small testes, although most have normal-sized or even large testis, decreased spermatogenesis, spermatogenic arrest, subfertility and sterility have been reported ( 59 , 60 , 61 ). It appears that XY pairing and recombination usually occur normally in 47,XYY, with the extra Y chromosome being lost during spermatogenesis ( 62 , 63 ), so that many 47,XYY men have fathered chromosomally normal children. In trisomy X syndrome, premature ovarian failure (primary ovarian insufficiency) is more prevalent than in controls ( 55 , 64 ), and there are many case reports of both primary and secondary amenorrhea.…”