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A novel 5q11.2 deletion detected by microarray comparative genomic hybridisation in a child referred as a case of suspected 22q11 deletion syndrome

Human Genetics volume 116, pages 83–90 (2005)Cite this article

Abstract

The 22q11 deletion syndrome (22q11DS) is a developmental syndrome comprising of heart, palate, thymus and parathyroid glands defects. Individuals with 22q11DS usually carry a 1.5- to 3-Mb heterozygous deletion on chromosome 22q11.2. However, there are many patients with features of 22q11DS without a known cause from conventional karyotype and FISH analysis. Six patients with features of 22q11DS, a normal chromosomal and FISH 22q11 analysis, were selected for investigation by microarray genomic comparative hybridisation (array CGH). Array-CGH is a powerful technology enabling detection of submicroscopic chromosome duplications and deletions by comparing a differentially labelled test sample to a control. The samples are co-hybridised to a microarray containing genomic clones and the resulting ratio of fluorescence intensities on each array element is proportional to the DNA copy number difference. No chromosomal changes were detected by hybridisation to a high resolution array representing chromosome 22q. However, one patient was found to have a 6-Mb deletion on 5q11.2 detected by a whole genome 1-Mb array. This deletion was confirmed with fluorescence in-situ hybridisation (FISH) and microsatellite marker analysis. It is the first deletion described in this region. The patient had tetralogy of Fallot, a bifid uvula and velopharyngeal insufficiency, short stature, learning and behavioural difficulties. This case shows the increased sensitivity of array CGH over detailed karyotype analysis for detection of chromosomal changes. It is anticipated that array CGH will improve the clinician’s capacity to diagnose congenital syndromes with an unknown aetiology.

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Acknowledgements

We thank Heike Fiegler and Chiara Bacchelli for technical support and the Wellcome Trust Sanger Institute Microarray Core Facility for printing the microarrays. This work is funded by the Wellcome Trust.

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Authors and Affiliations

  1. Molecular Medicine Unit, Institute of Child Health, University College London, 30, Guilford Street, London, WC1N 1EH, UK

    Katrina Prescott & Peter Scambler

  2. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Kathryn Woodfine & Nigel P. Carter

  3. North East London Regional Cytogenetics Laboratory, Great Ormond Street Hospital, London, UK

    Paula Stubbs & Rodger Palmer

  4. Royal Manchester Children’s Hospital, Hospital Road, Pendlebury, Manhester, UK

    Maurice Super & Bronwyn Kerr

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  1. Katrina Prescott
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  2. Kathryn Woodfine
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  3. Paula Stubbs
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  4. Maurice Super
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  5. Bronwyn Kerr
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  6. Rodger Palmer
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  7. Nigel P. Carter
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  8. Peter Scambler
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Correspondence to Peter Scambler.

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Prescott, K., Woodfine, K., Stubbs, P. et al. A novel 5q11.2 deletion detected by microarray comparative genomic hybridisation in a child referred as a case of suspected 22q11 deletion syndrome. Hum Genet 116, 83–90 (2005). https://doi.org/10.1007/s00439-004-1195-6

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  • DOI: https://doi.org/10.1007/s00439-004-1195-6

Keywords

  • Copy Number Change
  • 22q11 Deletion Syndrome
  • Chromosome Metaphase Spread
  • Microsatellite Marker Analysis
  • Velopharyngeal Insufficiency