Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype

Carolina Sismani¹ , Sofia Kitsiou-Tzeli² , Marios Ioannides¹ , Christodoulos Christodoulou¹ , Violetta Anastasiadou³ , Goula Stylianidou³ , Eleftheria Papadopoulou⁴ , Emanuel Kanavakis² , Zoe Kosmaidou-Aravidou⁵ and Philippos C Patsalis¹

¹Department of Cytogenetics, The Cyprus Institute of Neurology and Genetics Nicosia, Cyprus

²Department of Medical Genetics, University of Athens, Choremio Research Laboratory, "Aghia Sophia" Children's Hospital, Athens, Greece

³Department of Pediatrics, Arch Makarios III Hospital, Nicosia, Cyprus

⁴Department of Paediatrics, University Hospital of Heraklion, Crete, Greece

⁵Department of Genetics, Alexandra Hospital, Athens, Greece

author email corresponding author email

Molecular Cytogenetics 2008, 1:15doi:10.1186/1755-8166-1-15


Published:	21 July 2008

Abstract

Background

Carriers of apparently balanced translocations are usually phenotypically normal; however in about 6% of de novo cases, an abnormal phenotype is present. In the current study we investigated 12 patients, six de novo and six familial, with apparently balanced translocations and mental retardation and/or congenital malformations by applying 1 Mb resolution array-CGH. In all de novo cases, only the patient was a carrier of the translocation and had abnormal phenotype. In five out of the six familial cases, the phenotype of the patient was abnormal, although the karyotype appeared identical to other phenotypically normal carriers of the family. In the sixth familial case, all carriers of the translocations had an abnormal phenotype.

Results

Chromosomal and FISH analyses suggested that the rearrangements were "truly balanced" in all patients. However, array-CGH, revealed cryptic imbalances in three cases (3/12, 25%), two de novo (2/12, 33.3%) and one familial (1/12, 16.6%). The nature and type of abnormalities differed among the cases. In the first case, what was identified as a de novo t(9;15)(q31;q26.1), a complex rearrangement was revealed involving a ~6.1 Mb duplication on the long arm of chromosome 9, an ~10 Mb deletion and an inversion both on the long arm of chromosome 15. These imbalances were located near the translocation breakpoints. In the second case of a de novo t(4;9)(q25;q21.2), an ~6.6 Mb deletion was identified on the short arm of chromosome 7 which is unrelated to the translocation. In the third case, of a familial, t(4;7)(q13.3;p15.3), two deletions of ~4.3 Mb and ~2.3 Mb were found, each at one of the two translocation breakpoints. In the remaining cases the translocations appeared balanced at 1 Mb resolution.

Conclusion

This study investigated both de novo and familial apparently balanced translocations unlike other relatively large studies which are mainly focused on de novo cases. This study provides additional evidence that cryptic genomic imbalances are common in patients with abnormal phenotype and "apparently balanced" translocations not only in de novo but can also occur in familial cases. The use of microarrays with higher resolution such as oligo-arrays may reveal that the frequency of cryptic genomic imbalances among these patients is higher.