Chromosome segregation in an infertile man carrying a unique pericentric inversion, inv(21)(p12q22.3), analysed using fluorescence in situ hybridization on sperm nuclei: significance for clinical genetics. A case report.

We report the case of a 40-year-old patient referred to our centre after 3 years of infertility. Karyotyping with the aid of fluorescence in situ hybridization (FISH) analysis showed a unique pericentric inversion of chromosome 21:46,XY,inv(21)(p12q22.3). This type of intrachromosomal structural rearrangement can lead to chromosome imbalance in offspring by producing unbalanced gametes if an odd number of crossover events occur within the inverted segment. Therefore, partial trisomy/monosomy with clinical consequences can be observed in the progeny of carriers. Semen samples from the inversion carrier were analysed by FISH using a combination of probes [a subtelomeric 21q probe and a locus-specific Down's syndrome critical region (DSCR) probe] to evaluate the proportion of recombinant chromosomes. Sperm-FISH analysis of 3400 spermatozoa revealed a 67.4% rate of balanced chromosomes (normal or inverted). The frequencies of recombinant chromosomes with duplication of the long arm and deletion of the short arm, and vice versa, were 11.2 and 21.4%, respectively. The risk for the couple of conceiving a child with an unbalanced chromosome 21 is estimated to be around 32%. This case study shows the utility of sperm-FISH analysis in the genetic counselling of a pericentric inversion in a male carrier to assess the frequency of recombinant chromosomes and therefore evaluate the probability of having a normal conception.