Nonmosaic balanced homologous translocations of major clinical significance: some may be mosaic.

The main mechanism proposed for formation of homologous translocations/isochromosomes is mitotic and if this occurs in a chromosomally normal conceptus, mosaicism would be expected to be seen. The lack of mosaicism in published cases of rearrangement (REA) of mitotic origin might be explained by under-detection due to the low level mosaicism for a normal line. Recently it was reported that sex-specific centromere instability in early embryogenesis leads to a female prevalence among individuals with mosaicism for pericentromeric rearrangements. To determine whether carriers of apparent non-mosaic homologous REA could be mosaics for a normal cell line, the sex ratio (male to female ratio) among carriers of balanced and unbalanced homologous translocations/isochromosomes was studied. This ratio was determined to establish if there is a female predominance similar to that seen in carriers of REA with mosaicism. In reviewing the literature, a female prevalence among fetuses with balanced homologous REA and among carriers of unbalanced homologous REA detected prenatally, postnatally and in miscarriages was found. Overall, there were 48 males and 72 females in the collected sample, and this ratio differed significantly from the expected sex ratio of 1.06 (P = 0.0075). There is not a male prevalence among miscarried fetuses, there is no evidence of selection against males in the collected material of this study. The analysis of sex ratios in different variants of trisomy 13 with respect to ascertainment (prenatal diagnosis, miscarriages, liveborn) also does not support an intrauterine selection against males as a cause of a female prevalence among carriers of homologous REA. Thus the data presented in this paper suggests that a proportion of the carriers of balanced homologous REA may have mosaicism for a normal line. Since low level mosaicism for a normal line in a translocation carrier would alter his/her reproductive options, it can be recommended that molecular polymorphic analysis be applied to these cases. This would allow those resulting from meiotic formation to be distinguished from those resulting from postzygotic formation. This latter mechanism may indicate the presence of a mosaicism for a normal line, making further intensive karyotypic analysis advisable. However, additional studies of healthy carriers of homologous REA of chromosome 14 or 15 should not be done. (c) 2007 Wiley-Liss, Inc.