1. ¹Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
2. ²Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
3. ³Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
4. ⁴Location Juliana Kinderziekenhuis, Hagaziekenhuis, Den Haag, The Netherlands
5. ⁵Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

Correspondence: Dr K Szuhai, Department of Molecular Cell Biology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, zone S-1–P, The Netherlands. Tel: +31 71 5269211; Fax: +31 71 5268270; E-mail: k.szuhai@lumc.nl

Received 16 August 2006; Revised 31 January 2007; Accepted 7 February 2007; Published online 7 March 2007.

Abstract

Ring chromosomes are rare cytogenetic findings and are associated at phenotypic level with mental retardation and congenital abnormalities. Features specific for ring chromosome syndromes often overlap with the features of terminal deletions for the corresponding chromosomes. Here, we report a case of a ring chromosome 14 which was identified by conventional cytogenetics and shown to have a terminal deletion and an additional inverted duplication with a triplication by using large insert clone and oligo array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA). The combination of an inverted duplication with a terminal deletion in a ring chromosome is of special interest for the described syndromes of chromosome 14. The presented findings might explain partly overlapping clinical features described in terminal deletion, duplication and ring chromosome 14 cases, as these rearrangements can be easily overlooked when performing GTG-banding only. Furthermore, we suggest that ring chromosome formation can act as an alternative chromosome rescue next to telomere healing and capture, particularly for acrocentric chromosomes. To our knowledge, this is the first time an inverted duplication with a terminal deletion in a ring chromosome is identified and characterized using high-resolution molecular karyotyping. Systematic evaluation of ring chromosomes by array-CGH might be especially useful in distinguishing cases with a duplication/deletion from those with a deletion only.