Abstract

Introduction and methods: We report the screening of 41 de novo reciprocal translocations and 18 de novo complex chromosome rearrangements (CCRs) using array-CGH. All cases had been interpreted as "balanced" by conventional cytogenetics. Results: Twenty-seven cases of reciprocal translocations were detected in patients with an abnormal phenotype and after array-CGH analysis eleven resulted unbalanced. Thus we found that 40% of patients with a “chromosomal phenotype” and an apparently balanced translocation were unbalanced (11 cases out of 27), and that 18% of the reciprocal translocations were instead complex rearrangements (5 cases out of 27) with more than three breakpoints. Fourteen fetuses with de novo apparently balanced translocations, all but two with normal ultrasound findings, were also analyzed and all resulted normal after array-CGH. Thirteen CCRs were detected in individuals with abnormal phenotypes, two in females with repeated abortions and three in fetuses. We found that sixteen were unbalanced with up to four deletions. Discussion: Our investigations suggest that genome-wide array-CGH may be recommendable in all carriers of "balanced" CCRs. The parental origin of the deletions was investigated in five reciprocal translocations and eleven CCRs. All resulted to be paternal. Using customized platforms in seven cases of CCRs, we narrowed down the deletion breakpoints to few-hundreds base pairs and no susceptibility motifs were associated with the imbalances. Our findings demonstrate that the phenotypic abnormalities of apparently balanced de novo CCRs are mainly due to cryptic deletions and that spermatogenesis is more prone to generate multiple chaotic chromosome imbalances and reciprocal translocations than oogenesis.