The Journal of Pediatrics
Volume 156, Issue 5 , Pages 810-817.e4 , May 2010

Array Comparative Genomic Hybridization as a Diagnostic Tool for Syndromic Heart Defects

  • Jeroen Breckpot, MD

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • These authors contributed equally.
    • ,
  • Bernard Thienpont, PhD

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • These authors contributed equally.
    • ,
  • Hilde Peeters, MD, PhD

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Thomy de Ravel, MD, PhD

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Amihood Singer, MD

      Affiliations

    • Clinical Genetics, Kaplan Medical Center, Rehovot, Israel
    • ,
  • Maissa Rayyan, MD

      Affiliations

    • Neonatology Unit, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Karel Allegaert, MD, PhD, Prof

      Affiliations

    • Neonatology Unit, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Christine Vanhole, MD, PhD, Prof

      Affiliations

    • Neonatology Unit, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Benedicte Eyskens, MD, PhD, Prof

      Affiliations

    • Department of Pediatric and Congenital Cardiology, University Hospital Gasthuisberg, Leuven, Belguim
    • ,
  • Joris Robert Vermeesch, PhD, Prof

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Marc Gewillig, MD, PhD, Prof

      Affiliations

    • Pediatric Cardiology Unit, University Hospitals Leuven, Leuven, Belgium
    • ,
  • Koenraad Devriendt, MD, PhD, Prof

      Affiliations

    • Center of Human Genetics, University Hospitals Leuven, Leuven, Belgium
    • Corresponding Author InformationReprint requests: Prof Dr Koenraad Devriendt, Center of Human Genetics, University Hospitals Leuven, Herestraat 49 bus 602, B-3000 Leuven, Belgium.
    • These authors contributed equally.

Received 29 June 2009 ,Revised 10 October 2009 ,Accepted 13 November 2009.

References 

  1. Lee C, Iafrate AJ, Brothman AR. Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet. 2007;39:S48–S54
  2. van Karnebeek CD, Hennekam RC. Associations between chromosomal anomalies and congenital heart defects: a database search. Am J Med Genet. 1999;84:158–166
  3. Meberg A, Hals J, Thaulow E. Congenital heart defects—chromosomal anomalies, syndromes and extracardiac malformations. Acta Paediatr. 2007;96:1142–1145
  4. Thienpont B, Mertens L, de Ravel T, Eyskens B, Boshoff D, Maas N, et al. Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients. Eur Heart J. 2007;28:2778–2784
  5. Krepischi-Santos AC, Vianna-Morgante AM, Jehee FS, Passos-Bueno MR, Knijnenburg J, Szuhai K, et al. Whole-genome array-CGH screening in undiagnosed syndromic patients: old syndromes revisited and new alterations. Cytogenet Genome Res. 2006;115:254–261
  6. Richards AA, Santos LJ, Nichols HA, Crider BP, Elder FF, Hauser NS, et al. Cryptic chromosomal abnormalities identified in children with congenital heart disease. Pediatr Res. 2008;64:358–363
  7. Frias JL, Carey JC. Mild errors of morphogenesis. Adv Pediatr. 1996;43:27–75
  8. Marden PM, Smith DW, McDonald MJ. Congenital anomalies in the newborn infant, including minor variations. A study of 4412 babies by surface examination for anomalies and buccal smear for sex chromatin. J Pediatr. 1964;64:357–371
  9. Menten B, Maas N, Thienpont B, Buysse K, Vandesompele J, Melotte C, et al. Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports. J Med Genet. 2006;43:625–633
  10. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, et al. Detection of large-scale variation in the human genome. Nat Genet. 2004;36:949–951
  11. Maas NM, Van Buggenhout G, Hannes F, Thienpont B, Sanlaville D, Kok K, et al. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridization (CGH). J Med Genet. 2008;45:71–80
  12. Hannes FD, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, Breuning MH, et al. Recurrent reciprocal deletions and duplications of 16p13.11: The deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J Med Genet. 2008;46:223–232
  13. Mefford HC, Cooper GM, Zerr T, Smith JD, Baker C, Shafer N, et al. A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease. Genome Res. 2009;19:1579–1585
  14. Itsara A, Cooper GM, Baker C, Girirajan S, Li J, Absher D, et al. Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. 2009;84:148–161
  15. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, et al. Strong association of de novo copy number mutations with autism. Science. 2007;316:445–449
  16. Thienpont B, de Ravel T, Van Esch H, Van Schoubroeck D, Moerman P, Vermeesch JR, et al. Partial duplications of the ATRX gene cause the ATR-X syndrome. Eur J Hum Genet. 2007;15:1094–1097
  17. Breckpot J, Takiyama Y, Thienpont B, Van Vooren S, Vermeesch JR, Ortibus E, et al. A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay. Eur J Hum Genet. 2008;16:1050–1054
  18. Balikova I, Lehesjoki AE, de Ravel TJ, Thienpont B, Chandler KE, Clayton-Smith J, et al. Deletions in the VPS13B (COH1) gene as a cause of Cohen syndrome. Hum Mutat. 2009;30:E845–E854
  19. Roos A, Elbracht M, Baudis M, Senderek J, Schonherr N, Eggermann T, et al. A 10.7 Mb interstitial deletion of 13q21 without phenotypic effect defines a further non-pathogenic euchromatic variant. Am J Med Genet A. 2008;146A:2417–2420
  20. Brewer C, Holloway S, Zawalnyski P, Schinzel A, FitzPatrick D. A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality—and tolerance of segmental aneuploidy—in humans. Am J Hum Genet. 1999;64:1702–1708
  21. Manolio TA. Cohort studies and the genetics of complex disease. Nat Genet. 2009;41:5–6
  22. de Vries BB, White SM, Knight SJ, Regan R, Homfray T, Young ID, et al. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet. 2001;38:145–150
  23. Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38:452–457
  24. Zweier C, Albrecht B, Mitulla B, Behrens R, Beese M, Gillessen-Kaesbach G, et al. “Mowat-Wilson” syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene. Am J Med Genet. 2002;108:177–181
  25. Greenway SC, Pereira AC, Lin JC, DePalma SR, Israel SJ, Mesquita SM, et al. De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat Genet. 2009;41:931–935
  26. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med. 2008;359:1685–1699
  27. Sarri C, Gyftodimou Y, Grigoriadou M, Pandelia E, Kalogirou S, Kokotas H, et al. Supernumerary marker chromosome 5 diagnosed by M-FISH in a child with congenital heart defect and unusual face. Cytogenet Genome Res. 2006;114:330–337
  28. Cardoso C, Boys A, Parrini E, Mignon-Ravix C, McMahon JM, Khantane S, et al. Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion. Neurology. 2009;72:784–792
  29. Bisgaard AM, Kirchhoff M, Tumer Z, Jepsen B, Brondum-Nielsen K, Cohen M, et al. Additional chromosomal abnormalities in patients with a previously detected abnormal karyotype, mental retardation, and dysmorphic features. Am J Med Genet A. 2006;140:2180–2187
  30. Schneider A, Benzacken B, Guichet A, Verloes A, Bonneau D, Collot N, et al. Molecular cytogenetic characterization of terminal 14q32 deletions in two children with an abnormal phenotype and corpus callosum hypoplasia. Eur J Hum Genet. 2008;16:680–687
  31. Ellinor PT, Sasse-Klaassen S, Probst S, Gerull B, Shin JT, Toeppel A, et al. A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26. J Am Coll Cardiol. 2006;48:106–111
  32. Marangi G, Leuzzi V, Orteschi D, Grimaldi ME, Lecce R, Neri G, et al. Duplication of the Rubinstein-Taybi region on 16p13.3 is associated with a distinctive phenotype. Am J Med Genet A. 2008;146A:2313–2317
  33. Thienpont B, Breckpot J, Holvoet M, Vermeesch JR, Devriendt K. A microduplication of CBP in a patient with mental retardation and a congenital heart defect. Am J Med Genet A. 2007;143A:2160–2164
  34. Maclean K, Smith J, St Heaps L, Chia N, Williams R, Peters GB, et al. Axenfeld-Rieger malformation and distinctive facial features: clues to a recognizable 6p25 microdeletion syndrome. Am J Med Genet A. 2005;132:381–385
  35. Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, et al. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. J Med Genet. 2008;45:710–720

 Supported by grants from the FWO (FWOG.0254.05) and the Belgian program of Interuniversity Poles of attraction (GOA/2006/12). K.D. is a senior clinical investigator and J.B. is an aspirant investigator of the FWO Vlaanderen. B.T. is supported by a grant from the IWT Vlaanderen. The other authors declare no conflicts of interest.

PII: S0022-3476(09)01158-5

doi: 10.1016/j.jpeds.2009.11.049

The Journal of Pediatrics
Volume 156, Issue 5 , Pages 810-817.e4 , May 2010

Article Tools

* Image Usage & Resolution