Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions.

BACKGROUND: Mosaicism for an autosomal structural rearrangement (Rea) associated with clinical manifestation of chromosomal imbalance is rare. Consequently, there is a lack of basic epidemiological characterization of this kind of mosaicism, such as population rate, cytogenetic profile of Reas involved, maternal age distribution, and sex (male to female) ratio among Rea carriers. The objectives of the present study were: (i) determination of the Rea profile in clinically affected individuals, (ii) comparative analysis of the cytogenetic profile and involvement of single chromosomes to rearrangements in affected and previously reported asymptomatic carriers, (iii) analysis of the male/female ratio in carriers of various types of Rea, and, (iv) examination of parental ages distributions according to carriers' sex.

RESULTS: Two hundred and forty six disease-defined cases of mosaicism for autosomal non-centromeric Rea with a normal cell line of known sex were identified from the literature. There was a significant difference in single chromosome involvements compared to structural rearrangements between affected and asymptomatic carriers of unbalanced Rea, p =0.0030. In affected carriers, chromosome 18 was most frequently involved in structural rearrangements (12.6% of 246 instances). The least frequently rearranged were chromosomes 16 and 21 (0.8% and 1.2%, respectively). In asymptomatic carriers, the most frequently rearranged were chromosomes 5 and 21 (13% of 51 instances each). Among carriers of "loss" or "gain/loss" of genomic material, a female predominance was observed (50 M/89 F, different from population ratio of 1.06 at p = 0.0002). Carriers of either "gain" or balanced Rea demonstrated typical male predominance (41 M/30 F and 18 M/16 F), not different from 1.06. Maternal and paternal ages were reported in 129 and in 109 cases, respectively. There was a significant difference in maternal age distribution between male and female carriers, with mean maternal age of 25.2 years vs 28.3 years (p = 0.032). However, there was no difference in paternal age, with mean paternal age of 29.4 in both groups.

CONCLUSION: The data suggested that structural rearrangements of certain chromosomes involved in mosaicism may not be tolerated by the embryo, while others have higher survival prospects. Maternal age appears to be a risk factor for somatic mosaicism of structural Rea in female offspring or might cause an adverse effect on male embryo viability.