Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

Lars T Van Der Veken,Raoul Van De Graaf,Pino J Poddighe,A Jeannette M Hoogeboom,Hannie Douben,Annelies De Klein,Judith C Van De Brug,Marianne Mj Dieleman

doi:10.1186/1755-8166-3-13

Abstract

BackgroundSeveral cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity.ResultsWe report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BAC-probes located in the region indicated the presence of 6 signals on the r(18) chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy.ConclusionsWe report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11.

Highlights

Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18
In our patient a supernumerary ring chromosome 18 was detected in 13% of the metaphases of van der Veken et al Molecular Cytogenetics 2010, 3:13 http://www.molecularcytogenetics.org/content/3/1/13 peripheral blood lymphocytes
Small ring marker chromosomes have been shown to originate from the centromere and from the adjacent pericentric regions of a wide variety of chromosomes[6]

Summary

Introduction

Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Ring chromosomes 18 have been reported in a significant number of cases. In most cases the ring chromosome 18 replaces a normal maternal or paternal chromosome 18. Few cases have been described with supernumerary small ring chromosomes 18[3,4,5,6,7,8,9,10,11,12,13].

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