Further evidence for lack of association of PRDM9 polymorphisms and 22q11.2 deletion syndrome

Abstract

The 22q11.2 Deletion Syndrome (22q11.2DS) represents the most common recurrent deletion syndrome in humans. It results from Non-Allelic Homologous Recombination (NAHR) between sister chromatids or homologous chromosomes, favored by the presence of sequences of low copy repeats (LCRs) in the region. Additional events leading to the clustering in this region might be associated to proteins of the meiotic recombination mechanism acting as predisposing factors, as suggested for PRDM9. The aim of this study was to investigate polymorphisms in the PRDM9 gene in parents of individuals with the 22q11.2DS. The casuistry was composed of 31 family trios, including the index case and both parents, for which the parental origin of the 22q11 deletion was defined through microsatellite DNA markers analyses. The results were informative for 28 of the 31 families, for which 17 (61%) had maternal and 11 (39%) paternal origin. The genotyping of the PRDM9 for the 56 parents showed that 43 (77%) of them were homozygous, while the other 13 (23%) were heterozygous. Sequencing of the PRDM9 polymorphic region showed a genotypic distribution of 26 (60%) individuals A/A and 17 (40%) individuals N/N. Among the control group, represented by the non-transmitting parents, the frequency of allele A was 65%, while among the parents-of-origin it represented 55%, a difference with no statistical significance (p = 0.3811 Fisher's exact test). This study reinforces the lack of evidence for the association of the PRDM9 genotype as a susceptibility factor to the 22q11.2DS.