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Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region
  1. Anne Ronan1,
  2. Kerry Fagan2,
  3. Louise Christie1,
  4. Jeffrey Conroy3,
  5. Norma J Nowak3,4,
  6. Gillian Turner1
  1. 1Hunter Genetics Unit, Waratah, New South Wales, Australia
  2. 2Department of Cytogenetics, Hunter Area Pathology Service, New Lambton, New South Wales, Australia
  3. 3Microarray and Genomics Facility, Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, New York, USA
  4. 4Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, New York, USA
  1. Correspondence to:
 Dr A Ronan
 PO Box 437, The Junction, New South Wales 2291, Australia; aronan{at}


A 4.3 Mb duplication of chromosome 21 bands q22.13–q22.2 was diagnosed by interphase fluorescent in-situ hybridisation (FISH) in a 31-week gestational age baby with cystic hygroma and hydrops; the duplication was later found in the mother and in her 8-year-old daughter by the same method and confirmed by array comparative genomic hybridisation (aCGH). All had the facial gestalt of Down syndrome (DS). This is the smallest accurately defined duplication of chromosome 21 reported with a DS phenotype. The duplication encompasses the gene DYRK1 but not DSCR1 or DSCAM, all of which have previously been implicated in the causation of DS. Previous karyotype analysis and telomere screening of the mother, and karyotype analysis and metaphase FISH of a chorionic villus sample, had all failed to reveal the duplication. The findings in this family add to the identification and delineation of a “critical region” for the DS phenotype on chromosome 21. Cryptic chromosomal abnormalities can be missed on a routine karyotype for investigation of abnormal prenatal ultrasound findings, lending support to the use of aCGH analysis in this setting.

  • aCGH, array comparative genomic hybridisation
  • BAC, bacterial artificial chromosome
  • DS, Down syndrome
  • DSCR1, Down syndrome critical region 1
  • FISH, fluorescent in-situ hybridisation

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  • Published Online First 19 January 2007

  • Competing interests: None declared.

  • Informed consent was obtained for publication of fig 1 and fig 2.