Comparative genomic hybridization reveals a partial de novo trisomy 6q23-qter in an infant with congenital malformations: delineation of the phenotype.

We report the use of comparative genomic hybridization (CGH) to define the origin of a small extra segment (unidentifiable by classical cytogenetics) present in a de novo add(13)q34 chromosome that we found in the karyotype of a newly born boy with congenital heart defects, brain anomalies and dysmorphic signs. Initial investigation with fluorescence in situ hybridization (FISH) and a chromosome-13-specific library revealed that the excess material was not derived from chromosome 13. To uncover the origin of the unknown chromosome material, CGH was carried out on DNA isolated from blood lymphocytes of the patient. By using a conventional fluorescence microscope with no digital imaging devices, a single distinct region with gain of fluorescent intensity was observed on distal chromosome 6q. Confirmation of this finding by FISH with a chromosome-6-specific paint and a subtelomeric yeast artificial chromosome clone from 6q26-q27, in combination with the band morphology of the small extra chromosomal segment, allowed us to diagnose the additional material as being derived from chromosome 6q23-qter. FISH with a telomere 13q probe detected a terminal deletion of 13q34-qter on the derivative chromosome 13, indicating that the der(13) was a result of a translocation event. Genotyping of the hypervariable apolipoprotein (a) gene, which lies within 6q26-q27, showed that the additional chromosome 6 material was inherited from the mother. The karyotype of the proposita is therefore: 46,XY,-13,+der(13)t(6;13)(q23;q34) de novo (mat). Our results confirm the usefulness of CGH as an attractive alternative method for the characterization of constitutional small genetic imbalances and contribute to the delineation of the trisomy 6q23-qter phenotype.