Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients

Abstract

We report molecular cytogenetic characterization of ring chromosome 15 in three unrelated male patients with the karyotype 46,XY,r(15). One was a stillborn child with several malformations, and the other two cases showed pre- and postnatal growth retardation and developmental delay, common features for ring chromosome 15 syndrome. One of these patients also displayed clinical features resembling Prader-Willi syndrome (PWS). To delineate the extent of the deletion on chromosome 15, we have carried out fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) mapping to the distal long arm of chromosome 15. The deletion breakpoints clustered within a 4.5-6.5 Mb region proximal to the 15q telomere. Two deletions involved the same known genes, while the largest deletion observed in the stillborn child involved three additional genes, including the COUP-TFII gene, which has been suggested to play a role in heart development. The heart malformations, which are observed in this patient, are thus likely to be due to hemizygosity/haploinsufficiency of the COUP-TFII gene. In all three patients, the insulin-like growth factor I receptor gene (IGF1R) gene was deleted supporting the association between IGF1R and growth retardation seen in ring chromosome 15 syndrome.

Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities

“…Several published reports have examined smaller cohorts of patients with complex clinical presentations and described non-recurrent contiguous gene deletion syndromes contributing to CVMs, including 1p36 monosomy, 30 15q26 deletion, [31][32][33][34][35] Wolf-Hirschhorn syndrome (4p16.3 deletion), 36 Cri-du-chat syndrome (5p15.2 monosomy), 37 Miller-Dieker lissencephaly syndrome (17p13.3 deletion) 38 and 17q23.1q23.2 microdeletion syndrome. 18 Examples where such an approach was successful in identifying specific dosage-sensitive genes include JAG1 in Allagile Figure 1 Variable de novo (DN) deletions of 16q24.3 observed in multiple subjects with CVMs and ECAs.…”

Ring chromosome instability evaluation in six patients with autosomal rings

“…Usually the phenotype of ring chromosome patients overlaps that of the deletion of both ends of the respective chromosome syndromes (Schinzel, 2001). Nevertheless, the phenotypes associated with ring chromosomes are highly variable, since -in addition to the primary deletions associated with ring formation -secondary loss or gain of material may have occurred, due to the instability of ring chromosomes in general (Tümer et al, 2004;Purandare et al, 2005;Glass et al, 2006;Höckner et al, 2008;Zollino et al, 2009). Thus, the phenotype will actually depend on the size of the ring chromosome, the amount of euchromatin lost during ring formation, the ring stability, the presence of secondary aneuploid cells, and the rate of mosaicism (Kosztolányi, 1987a;Le Caigne et al, 2004).…”

Ring chromosome 15 presenting as short stature, intellectual disability and caf and eacute;-au-lait spots

“…Mosaic children may have less severe involvement. 3,5 Effect on growth is due to loss of particular gene called IGF-1r near the end of long arm of chromosome 15. More proximal the defect, severe the retardation.…”

“…More proximal the defect, severe the retardation. 2,5 Other causes of café-au-lait spots with mental retardation are Russell silver syndrome (RSS), tuberous sclerosis, fanconi anemia, ataxia telangiectasia and McCune Albright syndrome which are excluded by clinical signs and symptoms. RSS and Chromosome 15 Ring may share several features, including growth retardation and short stature, a triangular-shaped face, finger abnormalities, cafe-au-lait spots, and other abnormalities.…”