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Ring chromosome 15: characterization by array CGH

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Abstract

Ring chromosome 15 [r(15)] is an uncommon finding with less than 50 patients reported. Precise genotype–phenotype correlations are problematic because of the difficulties in determining the extent of euchromatic loss, the level of mosaicism, and the influence of the timing of ascertainment. We report two discordant examples of r(15) patients. In the first case, prenatal diagnosis of a de novo r(15) was made during the second trimester: mos 46,XX,r(15)(p11.2q26)[32]/45,XX,-15[13]/47,XX,r(15)(p11.2q26)x2[3]/46,XX,dic r(15)(p11.2q26p11.2q26[1]/46,XX[2]. Postnatal follow-up revealed extremely small stature, heart defects, and developmental delay. Patient 2 was a 31-year-old short-statured female who was living independently: 46,XX,r(15)(p11q26). Both cases showed loss of the 15q subtelomeric region by fluorescence in situ hybridization (FISH). To investigate the discordance in phenotypes between the two patients, we undertook array comparative genomic hybridization (array CGH) analyses to more fully characterize the deletions associated with these otherwise structurally indistinguishable r(15) chromosomes from conventional cytogenetic analyses and fluorescence in situ hybridization (FISH) studies. By array CGH, patient 1 showed deletion of multiple contiguous clones predicting an approximately 6 Mb deletion of distal 15q. In contrast, patient 2 showed loss of just the 15q subtelomeric clone and an interstitial clone by array CGH confirming that the severity of the phenotype correlated with the size of the deletion at the molecular level. These cases illustrate the utility of array CGH characterization for determining the size of the associated deletion in ring chromosomes and for facilitating phenotype–genotype correlations.

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Acknowledgements

We thank the patients and their families for their interest and willing and helpful cooperation. The authors are grateful to Richard Segraves and the Cytogenetics staff at Children’s Hospital and Research Center at Oakland, as well as Cytogenetics, Department of Pathology, Royal Brisbane Hospital, QLD, Australia for their expert technical assistance. This work was supported in part by NIH Grants HD048502 (K.A.R.), CA83040 (D.P.), and CA84118 (D.G.A).

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Authors and Affiliations

  1. Department of Pediatrics, University of Washington, M2-9, 4800 Sand Point Way NE, Seattle, WA, 98105, USA

    Ian A. Glass

  2. Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Katherine A. Rauen, Emily Chen & Philip D. Cotter

  3. Department of Genetics, Kaiser Permanente Medical Center, Oakland, CA, USA

    Emily Chen

  4. Queensland Clinical Genetics Service, Brisbane, QLD, Australia

    Jillian Parkes

  5. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA

    Donna G. Alberston & Daniel Pinkel

  6. Division of Medical Genetics, Department of Pathology, Children’s Hospital and Research Center at Oakland, 747 Fifty Second Street, Oakland, CA, USA

    Philip D. Cotter

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  1. Ian A. Glass
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  2. Katherine A. Rauen
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Correspondence to Ian A. Glass.

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Glass, I.A., Rauen, K.A., Chen, E. et al. Ring chromosome 15: characterization by array CGH. Hum Genet 118, 611–617 (2006). https://doi.org/10.1007/s00439-005-0030-z

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