Genomic complexity and complex chromosomal rearrangements in genetic diagnosis: example from two emblematic cases on chromosome 7

Abstract

Abstract Background. Complex chromosomal rearrangements are rare events compatible with survival, consisting in imbalance and/or position effect, which contribute to a range of clinical pictures. The investigation and diagnosis of these cases is often difficult and knowing the methodology followed in similar cases can be very useful for others. The interpretation of the results does not always lead to the mechanism’s identification and can potentially create critical communication problems for a possible recurrence. Here, we investigated two carriers of complex abnormality of chromosome 7 with a severe clinical picture. Case presentation. The first case was a 2-year-old girl with a pathological phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis we found a complex situation with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, 7p21.3p15.3). The second case was a newborn investigated for hypo development and dysmorphism. His karyotype showed a structurally altered chromosome 7. The maternal karyotype evidenced a structurally rearranged chromosome 7: the long arm region (7q11.23q22) was inserted in the short arm, at 7p15.3. The array-CGH analysis on the child identified an even more complex picture with a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb, between the 7q21.3 and the q22.1. The maternal array-CGH evidenced a trisomic portion corresponding to the tetrasomic region of the boy. Conclusions. Our work demonstrated, once again, that the support of both techniques is necessary to correctly interpret complex rearrangements. Finally, searching the literature and with bioinformatic tools, we found that segmental duplications, short interspersed elements (SINE) and long interspersed elements (LINE), may be responsible for these complex rearrangements.