Can one translocation impact the meiotic segregation of another translocation? A sperm-FISH analysis of a 46,XY,t(1;16)(q21;p11.2),t(8;9) (q24.3;p24) patient and his 46,XY,t(8;9)(q24.3;p24) brother and cousin

摘要

Individuals with two independent chromosome rearrangements are rare and meiotic segregation studies are few. Two brothers (P1 and P2) and a cousin (P3) were karyotyped and found to have the same familial reciprocal translocation between the long arm of chromosome 8 and the short arm of chromosome 9: 46,XY,t(8;9)(q24.3;p24). In addition, one brother also had a different de novo reciprocal translocation between the long arm of chromosome 1 and the short arm of chromosome 16: 46,XY,t(1;16)(q21;p11.2)dn,t(8;9)(q24.3;p24)mat. Using locus-specific probes for segments involved in the translocations and for other chromosomes, sperm-FISH analysis was used to investigate the products of meiotic segregation of the translocations and the possibility of an interchromosomal effect (ICE). Sperm nucleus fragmentation was also evaluated. For the t(8;9) translocation, the proportion of unbalanced products was higher for P1 (66.3%, P < 0.0001) than P2 (51.9%) and P3 (50.4%), and the proportion consistent with each meiosis I segregation mode was also different for P1. In addition, for P1, 61.6% of the products of the t(1;16) were unbalanced, and 85.6% of spermatozoa overall included both translocations. No evidence of an ICE was found and sperm nucleus fragmentation rates were similar. Our study suggests that co-segregation of the t(8;9) and the t(1;16) resulted in modifying the proportions of t(8;9) meiotic segregation products found in spermatozoa. This could be due to selection associated with meiotic checkpoints and germ cell death.