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Homologous Robertsonian Translocations: Spectrum, Sex Ratios, and Reproductive Risks

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Abstract

Robertsonian translocations/isochromosomes formed by homologous acrocentric chromosomes are rare, and consequently their epidemiology has not been well investigated. This study, based on the analysis of published data including systematic studies of patients with reproductive disorders and individual reports on carriers of homologous translocation (HT), was conducted to determine the major epidemiological characteristics of HT. 10-fold differences were found between couples with infertility and couples with miscarriages, both in the frequency of HT carriers (0.03 and 0.45‰, correspondingly) and in their proportion of the total number of robertsonian translocation carriers (0.9 and 9%, correspondingly), p < 0.005. In patients with an apparent male infertility factor, these rates are 0.21‰ and 3%. In the group of males from couples with miscarriages (although about half of them are partners of women with female factor of reproductive disorder), rates of 0.36‰ and 10.5% were observed, p < 0.05. Among all HT carriers, those with HT of chromosomes 13 and 22 are found more frequently. For carriers of HT of chromosomes 13, 14, 15 and 21, female predominance was typical with the average sex ratio (SR) of 0.36 (22♂/61♀). Among the carriers of chromosome 22 HT, there was no female predominance, SR = 1.18 (13♂/11♀) the difference with other acrocentrics is statistically significant, p < 0.05. Analysis of reports on individual cases showed that only two out of 22 male HT carriers, were tested for infertility. One of them had a cell line with unbalanced HT, and for the other patient, the researchers found no reason to link the impairment of spermatogenesis with the presence of HT. Thus, in the majority of male HT carriers, spermatogenesis was not impaired. It is suggested that the disturbance of spermatogenesis in some cases is due to gonadal mosaicism for translocation trisomy resulting from incomplete correction of the original translocation trisomy. There are some published reports on healthy offspring with an inherited a parental balanced HT and on offspring with normal karyotypes born to apparently non mosaic HT carriers. Hence, it is possible to consider the probability of having healthy offspring for HT carriers as not zero, therefore references to the algorithms for the patients’ comprehensive examination and appropriate counseling are given.

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Kovaleva, N.V. Homologous Robertsonian Translocations: Spectrum, Sex Ratios, and Reproductive Risks. Russ J Genet 55, 10–23 (2019). https://doi.org/10.1134/S1022795419010095

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